Polycomb body

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Shutdown of developmental genes by Polycomb bodies. Molecular complexes of the Polycomb group bind to regulatory segments of DNA (PRE) and aggregate within Polycomb bodies. The chromatin is strongly folded up. This shuts down the genes in this section of DNA.

Polycomb bodies ( English polycomb bodies, PcG bodies ) are protein complexes in the cell nucleus that have been detected in plants , flies (such as Drosophila ) and mammals , among others . They are probably bound to parts of the chromatin . After immunostaining , microscopically visible structures emerge within the cell nucleus. Their size and number vary within different cell types, and their distribution depends on the developmental state of the cell. They contain a high concentration of Polycomb proteins . These proteins from the Polycomb group are important factors that maintain the silence of developmental genes across multiple cell divisions . They are essential for the normal development of multicellular organisms. In mammals, they are involved in basic processes such as cellular memory , cell proliferation , genomic imprinting , X-inactivation and cancer development . In plants they are u. a. involved in cell differentiation and vernalization - the process by which blooming is accelerated by prolonged cold. The regulation of cell development by Polycomb proteins has been intensively researched using the model organism Drosophila melanogaster . The Polycomb proteins modify the histones of the chromatin in such a way that genes are inaccessible to the proteins of the cell's transcription machinery and thus practically shut down. This is called gene silencing . The thus decommissioned DNA sections collect in the Polycomb bodies. This shutdown can also be canceled later.

There are several models of the structure of the Polycomb bodies, which view them either as protein-based structures or as bodies made of chromatin. The Polycomb bodies move within the cell nucleus and thus connect different areas of the chromatin. Polycomb proteins are constantly exchanged within the Polycomb bodies.

introduction

Within eukaryotic cells, the cell nucleus contains the genetic material in the form of DNA , visible as chromatin . At any given point in time, however, only a part of the genes is required. This depends on the development cycle of the cell and the cell type. The cell has to make a choice as to which genes are active and which are not. The DNA of the genes that are not required is folded up compactly and forms the heterochromatin . The DNA wraps itself up compactly to form nucleosomes , is bound with other proteins and strongly compressed. The genes are therefore inaccessible to the enzymes that read them. With active genes, the chromatin is not so compact; DNA loops are formed from which the genes are read. In particular, the regulatory areas for genes such as promoters and enhancers for the regulatory proteins are accessible here. This three-dimensional organization of genes is important for regulating gene expression , i.e. how the information from the genes can be converted into proteins.

The central component of nucleosomes are the histone proteins, whose properties can be changed by binding other proteins. One of the functions of Polycomb proteins is to suppress the transcription of genes. This is done, among other things, by chemically changing the histone proteins . One of these changes is the methylation of some histones. A key part of DNA silencing is the methylation of histone # 3 (referred to as H3K27me3) within a nucleosome. This is done with the help of complexes made of Polycomb molecules.

During the development of an organism, the cells have to differentiate themselves differently . Different genes are active one after the other. This pattern of gene expression requires close control. This is supported by epigenetic mechanisms in that a cellular memory is built up, which is passed on in a stable manner to their daughter cells through replication and cell division . This has been intensively researched in the fruit fly Drosophila . Epigenetic regulators were discovered in the form of two groups of genes: The genes of the Polycomb group (PcG) and the Trithorax group (TrxG). The PcG and TrxG enzymes mediate the modification of the histones. The proteins of the Polycomb group can permanently silence a gene, while TrxG can activate genes.

The PcG proteins are not randomly distributed in the cell nucleus, but rather collect in several centers, the Polycomb bodies. They differ in size and number in different cell types; As a rule, there are fewer and larger bodies in undifferentiated cells, while in differentiated cells there are ever more and smaller bodies. They contain genes silenced by Polycomb proteins. Polycomb bodies move, meet, and divide dynamically as they develop. The number of these bodies per cell is between 12 and 16 and the diameter is 0.3–1.0 µm. Polycomb bodies differ in the size and amount of Polycomb proteins. In particular, PcG domains, i.e. DNA segments with a longer linear size, show a higher content of Polycomb proteins and produce larger Polycomb bodies.

Polycomb bodies have been observed in mammalian and Drosophila cell nuclei by immunostaining with antibodies against PcG proteins. Microscopic recordings or live imaging of fluorescence- labeled proteins showed that PcG proteins are localized in a relatively small number of Polycomb bodies.

With genome-wide analyzes using techniques such as chromosome conformation capture , the distribution of Polycomb proteins and the labeling of histones could be determined. The results suggest a hierarchical organization of the regulated genes. The first level consists of short individual regions of DNA bound by PcG proteins. These include the PREs (Polycomb Response Elements). These regions of DNA act as response elements necessary to recruit PcG proteins and shut down adjacent genes. The second level of this organization is determined by the clustering of individual PREs in Polycomb domains. These regions are marked with the histone H3K27me3 and partly by Polycomb proteins. These PREs can interact with each other to form three-dimensional structures. The Polycomb bodies are located on such a hierarchical organizational level of PcG domains. The Polycomb domains can mediate contacts across distant regions of DNA. This creates a network of Polycomb proteins and DNA. This creates chromatin loops with PcG-bound regulatory elements and the promoters of PcG target genes, the transcription of which is suppressed. PREs have been shown to be able to contact distant sites on the same or a different chromosome. These contacts are likely mediated by non-coding RNAs ( ncRNA ), isolators, or via RNA interference (RNAi).

Left picture: Sex comb of a male Drosophila leg . Right picture: mutated variant

In 1947, the first gene from the Polycomb group, Polycomb, was discovered in Drosophila melanogaster by Pamela Lewis. In Drosophila , male flies have a bristle structure on their first pair of legs, the so-called sex comb . This is used to hold the female in place during mating. The analysis of a fly mutant that has additional sexual combs on the second and third pair of legs ("polycomb") enabled the researchers to identify the first polycomb element (Pc).

Later, while studying homeotic genes, the role of Polycomb proteins as a negative regulator was discovered. These genes are necessary for proper body segmentation during development. A total of 18 PcG genes were in Drosophila discovered that the correct sequence of activation of the Hox - gene cluster regulate.

In plants, the existence of Polycomb bodies is difficult to prove. However, there are several indications that Polycomb components or their target genes cluster together in clusters. There the protein "LPH1", the functional plant homologue of Polycomb, suppresses gene expression. In the plant model organism Arabidopsis (thale cress), imaging methods were used to vary the distribution pattern of LHP1 in the nucleus from a uniform pattern in meristematic cells to several distinguishable foci in differentiated cells. This relationship between LHP1 distribution and the differentiation status of the cell is reminiscent of the connection between Polycomp bodies and cell differentiation in animals.

Proteins and DNA segments involved

PcG proteins

3D reconstruction of the human PRC2-AEBP2 complex

The proteins of the Polycomb group are important regulators of development that control the expression of hundreds of genes. Their activity is necessary to maintain an "epigenetic memory" of specific gene expression patterns. As epigenetic repressors, they have the important function of maintaining the memory of transcription programs during the development and differentiation of living beings. The gene silencing mediated by PcG proteins occurs in Polycomb bodies. The PcG components in the Polycomb bodies mediate the chromatin condensation of their target genes. This happens when several proteins of the PcG group combine to form molecular complexes (PRC1 and PRC2). These can modify the histones of the nucleosomes in such a way that they combine with the DNA that is wound onto them to form a compact chromatin structure. As a result, the genes contained therein are shut down, so to speak, since the DNA can no longer be read here (gene silencing). It has been shown that PcG complexes also condense chromatin in vitro and reduce DNA accessibility in vivo .

Most of the time, PcG proteins are diffusely distributed in the cell nucleus. However, in some cell types they also form bodies that are visible by fluorescence microscopy , regardless of the method by which they were taken. The distribution pattern of the PcG proteins and the associated histone markings depends on the cell type.

PcG proteins can also mediate their activity on different chromosomes through interactions across sections of DNA that are actually very distant. This is the basis so that gene expression can be coordinated spatially and temporally. The three-dimensional organization of PcG proteins contributes significantly to their function. With the help of PcG proteins, intra- and even interchromosomal interactions are established over long distances between PcG targets within the cell nucleus. This creates a high degree of chromatin organization in the 3D core space. These contacts from distant stretches of DNA could be mediated by non-coding RNAs, isolators, DNA elements, and RNAi machines.

In Drosophila there are specific regulatory stretches of DNA called Polycomb Group Response Elements (PREs). The PcG protein complexes bind the DNA at these points. Studies with Drosophila provided experimental evidence for sequential binding of PcG complexes to these PREs. For example, PcG proteins shut down the Hox genes by binding to cis -regulating DNA modules.

The antagonists of the PcG proteins are the proteins of the Trithorax (TrxG) group. They work on several hundred developmentally relevant target genes antagonistic to the proteins of the Polycomb group in order to maintain active transcription states. In general, proteins of the Polycomb group (PcG) work together with transcription repressors to maintain gene deactivation, while proteins of the trithorax group enable gene activation through appropriate transcription activators. The gene silencing by Polycomb proteins is stable over many cell generations and can only be overcome by germline differentiation processes.

The repressive functions of PcG are mostly associated with post-translational modifications of histones. This is followed by an inhibition of the chromatin remodeling and a compression of the chromatin. The enzyme complexes of PcG and TrxG work by binding to the regulatory regions of developmental genes such as PRE. In doing so, they regulate the complicated balance between the self-renewal of stem and progenitor cells and the implementation of cellular differentiation. In the course of differentiation, these regulatory regions bind one of these two protein complexes and are exclusively occupied by the proteins PcG or TrxG. This binding occurs depending on the cell line, so that the chromatin structure of these genes is fixed either in the active or in the silent state.

PRC1 / PRC2

Epigenetic silencing of genes mediated by PcG proteins. A) The DNA is wound up on histones and forms the nucleosomes with them. The histones themselves have arms made of protein threads (histone tail). This loose configuration of the chromatin can be read off by polymerase enzymes. B) H3K27 is triple methylated by the PRC2 protein complex. This allows PRC1 to bind to H2AK119. This leads to the condensation of the nucleosomes and thereby to the shutdown of the genes on this DNA segment. [1]

The various PcG proteins combine to form functionally different complexes that belong to two large families: the Polycomb repressive complexes 1 and 2 (PRC1 and PRC2). The molecular complexes of each family show catalytic activity. The amino acid sequence of PRC2 is evolutionarily more conserved than that of PRC1. Each complex is made up of several proteins with different biochemical functions, many of which are not well understood. Apparently, PcG complexes change the chromatin environment by modifying histones through their catalytic activity and also causing the chromatin to condense. In addition, PRC1 and PRC2 regulate the activity of RNA polymerase .

PRC1 contains the proteins Ph (Polyhomeotic), Psc (Posterior Sex Combs), Sce (Sex Comb Extra) / Ring and Pc (Polycomb). PRC2 contains Esc, Su (z) 12, p55 / CAF and the histone methyltransferase E (z). In mammals, however, the PRC1 complex has expanded considerably in the course of evolution, which has led to the existence of several orthologues per PRC1 component. Human cells encode five HPC (CBX), six PSC, three HPH and two SCE orthologues. The typical PRC1 complex contains a single representative from each gene family. All PRC1 protein complexes contain a core that is preserved in the most important animal lines and in plants, but not in fungi.

In the Arabidopsis plant , the protein "LIKE HETEROCHROMATIN PROTEIN1" (LHP1) is a functional homologue of Pc. There LHP1 colocalizes with the epigenetic markers throughout the genome and interacts with PRC1 and PRC2 members as well as with a long non-coding RNA. It is needed to suppress many Polycomb target genes in Arabidopsis.

These protein complexes mediate post-translational modifications of histone proteins. Modifications such as acetylation , methylation , phosphorylation and ubiquitination are carried out in order to generate a combinatorial " histone code ". This serves to regulate cell line-specific patterns of the chromatin structure during the entire development.

The PRC2 complex has histone methyl transferase activity. It trimethylates the histone H3 on lysine No. 27 (hence the abbreviation H3K27me3, "K" is the symbol for the amino acid lysine). PRC2 is required for selecting the genome region (here PRE) that is to be shut down. PRC1 is required to stabilize this shutdown. PRC1 acts by mediating the ubiquitination of the 119th lysine residue of histone H2A; this is achieved by two of the PRC1 proteins called ring finger proteins 1A and 1B. The monoubiquitination of lysine 119 on H2A and the di- / trimethylation of lysine 27 on H3 by PRC1 and PRC2 are supposed to block gene transcription directly.

This post-translational modification leads to the local chromatin structure being brought into a transcriptionally repressive state. Correct establishment of them is critical to the coordinated silence of genes throughout mammalian development.

Polycomb Response Element (PRE)

The Polycomb Response Elements (PREs) were discovered in Drosophila genes and defined as DNA fragments that cause the maintenance of the silenced expression of a transgene. PREs recruit the PRC2 complex, which triple methylates histone 3 of a nucleosome. This is a marker recognized by PcG proteins of the PRC1 complex to cause gene silencing. Overall, PREs can fulfill several tasks: They recruit proteins of the PcG and TrxG families. Depending on the status of promoters and enhancers, they assume an active or a deactivated state. They can maintain this state for a long time. However, the status can be changed again with new signals. The condition that was originally determined by transcription factors is retained . This maintenance can last for many cell generations, even if the initially determining transcription factors are missing. This enables PREs to deliver a stable epigenetic memory of both inactive and active transcription states. While the properties of PREs and the DNA sequences that define them are well characterized in Drosophila , their counterparts in mammals have proven elusive. Only a few PREs were identified there; however, 97% of PRC2 targets have been shown to correspond to CpG islands or similar CG-rich regions. In mammals, they represent PRE-like sequences that can recruit PcG and TrxG complexes. However, the PREs lack a consensus motive .

It has been shown that PREs of different PcG targets can interact with each other even over great distances, for example in Drosophila PcG proteins are recruited to chromatin via PRE sequences that can be several tens of kilobases away from their target genes.

Further investigations showed that PcG complexes that are bound to different PREs are neither necessary nor sufficient to mediate a long-range effect between the PcG binding sites. It has been shown that isolators, rather than PREs, mediate associations between PcG targets to form Polycomb bodies. Experiments also showed that an isolator placed between a PRE and a PcG target gene prevented the interaction between the PRE and the removed promoter. This blocked its shutdown. It can therefore be assumed that it is the isolator-binding proteins and not the PcG complexes that are responsible for the higher organization of PcG targets in the cell nucleus. With isolators, the chromatin conformation can be changed in such a way that chromatin loops are formed. With these loops, the isolator is able to bring an upstream PRE into contact with a downstream gene. On the other hand, PcG proteins also appear to contribute to the function of isolator proteins.

construction

Polycomb bodies are considered to be protein-based structures that are formed by the accumulation of PcG proteins. However, other studies show that they are viewed as a chromosomal domain rather than a protein-based core body. This is also suggested by kinetic experiments that show the complete recovery of PcG proteins outside the Polycomb bodies. Previous studies have found the same number of Polycomb bodies in the nucleus as the number of ribbons observed on polytene chromosomes . This suggests that Polycomb bodies are formed by PcG proteins that bind to their target chromatin. Some studies suggest that Polycomb bodies serve as the host variety for PcG target genes. Electron microscopy showed that Polycomb bodies correspond to areas that consist of condensed chromatin threads approx. 100 nm thick. In addition, there are genes that bind PcG: It is expected that the PcG target genes are another component of the Polycomb body. However, the significance of these components for the structural basis is quite controversial. The sections of DNA that bind to PcG proteins form loops from their chromosomal context and are located in the protein-based Polycomb bodies. The genes present there are shut down there. This suggests that the DNA loops are using the Polycomb bodies as dormant factories, rather than structurally building them up.

There are three models for building Polycomb bodies that take into account the points just mentioned:

A) A Polycomb body is formed like a typical core body, based on proteins. It is formed by an accumulation of PcG proteins and is located in the interchromatin compartment (see chromosome territory ).

B) Polycomb bodies form a collection of DNA-rich chromatin. The PcG proteins are bound to this DNA.

C) The Polycomb body is made up of a collection of Polycomb proteins bound to their target genes. These genes form loops out of their chromatin context. The Polycomb body is localized here in the Euchromatin .

Polycomb bodies colocalize with the histone H3K27me3 and form small core domains of varying intensity. Polycomb bodies are not among the most densely packed chromatin parts of the euchromatic part of the genome. This distribution of Polycomb bodies is consistent with an earlier study using electron microscopy that showed that Polycomb molecules are concentrated in the perichromatin compartment of the mammalian nucleus. In the cell nucleus, the decondensed perichromatin is located at the edge of the inactive chromatin. In addition, RNAs also appear to play an important role in PcG-mediated gene shutdown. For example, RNAi components were found to be important for the clustering of PREs or the function of isolators. RNAs could be the important messenger substances and regulators of structural components of the PcG body.

dynamics

Film of a fly embryo in stage 15 of development. Chromatin domains (red) and polycomb bodies (green) form different structures that occasionally go through long-range coordinated movements. Visualization through fluorescent proteins H2B-RFP and PC- GFP .
Above: Structure of a DNA segment that can be regulated by Polycomb proteins. Isolator proteins such as CTCF bind to isolator regions. PcG proteins and also Trx proteins can bind to the PRE region. When a gene is silenced by PcG, it is brought to a Polycomb body by CTCF. If the gene is active, for example by binding Trx to the PRE region, then the DNA segment is taken to a transcription factory . [2]

The structural nature and function of Polycomb bodies and the composition of these bodies by different variants of the Polycomb proteins were investigated by various experiments. The kinetics of Polycomb proteins was also investigated. In general, Polycomb proteins have been shown to be rapidly exchanged in these bodies. This suggests that Polycomb bodies are made up of Polycomb proteins. Further analysis showed that the number of Polycomb bodies and the number of ribbons that are visible on polytene chromosomes are the same. The observed colocalization of PcG target genes with Polycomb bodies in diploid cells confirms this view. The dynamics of Polycomb proteins outside the Polycomb bodies appear to be higher than those inside the Polycomb bodies. The Polycomb proteins move more slowly in the body and there is greater variability in their movement.

Polycomb bodies move, meet, and divide dynamically as a cell develops. Your movement can be divided into two categories: a fast but severely restricted movement and a slower one. Within the faster speed range, Polycomb bodies move in volumes that are slightly larger than those of condensed chromatin domains. During slow movement, chromatin domains and polycomb bodies undergo coordinated extensive movements that can correspond to the movement of entire chromosome territories (the area within the cell nucleus that occupies a single chromosome).

Both movements gradually slow down during development, suggesting that regulation of chromatin dynamics may play an important role in maintaining gene silencing in differentiated cells. Time-lapse imaging of chromosomes has shown that some sections of the chromatin experience Brownian motion . However, the movement of each section was limited to a sub-region of the cell nucleus. The movement of chromosomal segments was described as consistent with a random walk . The rapid movement of polycomb bodies and chromatin domains observed during early embryogenesis decreases sharply in late developmental stages, suggesting a possible contribution of chromatin dynamics to maintaining stable gene silencing. Temperature also affects the movement of chromatin domains and Polycomb bodies. The movement of Polycomb bodies is less sensitive to temperature during embryogenesis, while the movement of chromatin domains is temperature dependent throughout embryogenesis.

The transcription factories can be seen as antagonists of the Polycomb bodies . These bind to active chromatin and accumulate transcription factors at one point so that transcription can proceed efficiently. There are several models that Polycomb target genes commute between Polycomb bodies when suppressed and to transcription factories when transcriptionally active.

Functions

Hierarchical organization of developmental genes

Individual chromosomes cover a specific region within the nucleus, the chromosome territories . With increasing dissolution, chromosomes consist of topologically associated domains (TADs). This could be determined by the chromosome confirmation capture technique, since certain sections of chromosomes react with each other more often than with more distant sections. These TADs are sharply demarcated from each other at the binding sites of isolators such as the CTCF protein. These TADs differ in terms of different types of histone modifications and chromatin accessibility. TADs in which transcription is actively carried out contain corresponding histone markers. Through this grouping of the chromatin, whole gene complexes can be switched to active or inactive. For example, after the differentiation of embryonic stem cells, the entire TAD structure and the position of the TAD boundaries are not changed. Only small rearrangements occur, which correlate with a redistribution of the markings of the histones, and thus activate and shut down parts of the chromatin. The PRE regions to which the Polycomb proteins are bound form such TADs with the help of the Polycomb body. The chromatin of active TADs is labeled with H3K4me3, inactive ones with the histone H3K27me3. This hierarchical network, which extends from the recruitment of PcG proteins to gene silencing, is widely accepted. Conformation capture studies have been carried out with plants, but the presence of TADs in the model organism Arabidopsis has not yet been clearly demonstrated; the results still depend on the resolution of the Hi-C methods used.

Hierarchical organization of the genome architecture of Drosophila

This hierarchical organization of the genome is shown on the right using a simplified representation of the analysis of the Drosophila genome:

  • Visualization of the HI-C data: This graphic shows the data that were determined with the Chromosome Confirmation Capture Analysis. Sections of DNA that react more frequently with one another are shown here in dark red. The genome could thus be broken down into active and non-active sections, so-called topologically associated domains.
  • These domains correspond to the different states of the chromatin. "Void" chromatin are disused areas of DNA that can no longer be read (heterochromatin). The DNA regions shut down by Polycomb proteins are also visible as inactive TADs. However, this shutdown can be canceled again.
  • Folding of the chromatin: The heterochromatin is so strongly condensed that it can no longer be read. When the Polycomb proteins are shut down, an inactive domain is also formed, so that the genes contained therein are not accessible. In the case of active TADs, loops form that can be easily read by enzymes such as RNA polymerase . In addition, the regulatory sections such as enhancers that can increase the transcription activity of the gene are easily accessible here. The TADs are bounded by binding sites for isolators.
  • Each chromosome takes up its own volume in the cell nucleus (chromosome territory, shown here schematically in different colors); however, these volumes partially overlap and allow interchromosomal interactions.

How is it ensured that repression is maintained even when cells divide? During the DNA replication , the parental histones are reapplied to the resulting DNA through post-translational modification. Newly synthesized histones provide the additional need for nucleosomes for the resulting DNA. With this coexistence of parental and new histones, the markings on parental histones could serve as a blueprint for modification of nearby new histones. The histone H3K27me3 could thus be viewed as an epigenetic trait that is kept stable at a specific location across cell divisions. However, detailed analyzes show that the exact spread of H3K27me3 requires a continuous modification of new histones and previously unchanged parental histones over several cell generations. Further research showed that histone labeling does not require H3K27me3 to be located in a specific position. It is enough that markings distributed over a certain area reach a threshold level in order to maintain the epigenetic state.

Gene suppression nodes

Examination of the localization of Polycomb proteins has shown that they are organized into Polycomb bodies, which are often located in the vicinity of pericentromeric heterochromatin. With the aid of high-resolution fluorescence in situ hybridization (FISH) and immunostaining of PcG proteins, the colocalization of PcG target genes in the Polycomb bodies was only revealed when the genes were shut down. In this context, Polycomb bodies have been referred to as gene silencing factories. In Drosophila melanogaster , Polycomb proteins shut down Hox genes by binding to cis-regulating DNA segments, the so-called Polycomb Response Elements (PREs). Exactly how Polycomb bodies function in mammalian systems has yet to be determined.

Sumoylation Center

The SUMO molecule is a ubiquitin- like protein that covalently binds to a variety of protein substrates and changes the properties of the modified proteins. The SUMO bond is essential to the viability of cells and organisms from yeast to mammals. It affects many biological processes, including cell cycle progression, maintenance of genome integrity, and transcription. The human PcG protein Pc2 has been shown to act as a SUMO E3 ligase by bringing together SUMO E2 (Ubc9) and the substrates (CtBP and CTCF). The Polycomb bodies could form sumoylation centers. In Caenorhabditis elegans , the PcG protein SOP-2 is sumoylated and contains RNA-binding motifs that are able to bind small RNAs. These are evolutionarily conserved in vertebrate PcG proteins. The zinc finger protein CTCF has also been shown to be recruited for Polycomb bodies and modified by SUMO.

Response to stressful situations

The repression mediated by Polycomb proteins could also play an important part in responding to stressful situations. If the cell is exposed to heat shock , this leads to widespread repression of the genes. This is mediated by Polycomb proteins. The genome is then substantially reorganized. In addition, the distribution of the Polycomb bodies changes: they are usually not located in the nucleolus . After a heat shock, they can be found in the entire nucleus, including the nucleolus.

Long-range pairing of genes

Polycomb bodies mediate contacts between widely spaced genes. How this long-distance pairing is carried out remains largely unknown. It has been suggested that PRE-containing PcG target genes dynamically localize to Polycomb bodies so that genes located in one Polycomb body can only linger for a certain time and then be integrated into another Polycomb body.

This process of "hopping" between Polycomb bodies could prevent PcG target genes randomly in karyoplasm diffuse, allows these genes but at the same time to explore parts of the core and stay on Polycomb body near other genes. Once the genes have converged, a strong association could be made through regulatory components.

Vernalization

The vernalization , the stimulation of flowering by a longer period of cold weather, includes a Polycomb-mediated epigenetic closure of the FLOWERING LOCUS--C gene ( FLC ) gene in Arabidopsis. Persistent cold promotes the switchover to a shutdown state.

Alleles of the FLC gene group together during the cold. This generally persists even after the plants are returned to a warm environment. This clustering depends on the Polycomb factors that are necessary for the silencing of the FLC genes. A well-defined sequence of events has been described that includes the influence of the PRC2 protein and another set of plant homeodomain proteins (PHD). This leads to a progressive accumulation of H3K27me3 proteins at the nucleation site with increasing exposure to cold. A cold-induced non-coding RNA called COLDAIR supports the recruitment of PRC2 here.

After the plants were placed in a warm environment again, PHD-PRC2 complexes spread over the entire gene, causing increased H3K27me3 accumulation over the entire locus. The amount of H3K27me3 quantitatively reflects the duration of exposure to cold.

Web links

Commons : Polycomb-group proteins  - collection of pictures, videos and audio files

See also

Individual evidence

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  2. ↑ Vincenzo Pirrotta: Polycomb Group Proteins. ISBN 0-12-809737-X , p. 61 ( limited preview in Google book search).
  3. ↑ Stefania Del Prete, Javier Arpón, Kaori Sakai, Philippe Andrey, Valérie Gaudin: Nuclear Architecture and Chromatin Dynamics in Interphase Nuclei of Arabidopsis thaliana . In: Cytogenetic and Genome Research . tape 143 , no. 1-3 , 2014, ISSN  1424-8581 , pp. 28–50 , doi : 10.1159 / 000363724 (English, karger.com [accessed on March 1, 2020]).
  4. ↑ Stefanie Rosa, Filomena De Lucia, Joshua S. Mylne, Danling Zhu, Nobuko Ohmido: Physical clustering of FLC alleles during Polycomb-mediated epigenetic silencing in vernalization . In: Genes & Development . tape 27 , no. 17 , September 1, 2013, ISSN  0890-9369 , p. 1845–1850 , doi : 10.1101 / gad.221713.113 , PMID 24013499 , PMC 3778238 (free full text) - (English).
  5. ↑ a b c d e f Stefania del Prete, Pawel Mikulski, Daniel Schubert, Valérie Gaudin: One, Two, Three: Polycomb Proteins Hit All Dimensions of Gene Regulation . In: Genes . tape 6 , no. 3 , July 10, 2015, ISSN  2073-4425 , p. 520-542 , doi : 10.3390 / genes6030520 , PMID 26184319 , PMC 4584315 (free full text) - (English, mdpi.com [accessed September 17, 2019]).
  6. ↑ a b c d e f g h i j k l m n o Thierry Cheutin, Giacomo Cavalli: Progressive Polycomb Assembly on H3K27me3 Compartments Generates Polycomb Bodies with Developmentally Regulated Motion . In: PLoS Genetics . tape 8 , no. 1 , January 19, 2012, ISSN  1553-7404 , p. e1002465 , doi : 10.1371 / journal.pgen.1002465 , PMID 22275876 , PMC 3262012 (free full text) - (English, plos.org [accessed on September 17, 2019]).
  7. ↑ M. Carmo-Fonseca, MT Berciano, M. Lafarga: Orphan Nuclear Bodies . In: Cold Spring Harbor Perspectives in Biology . tape 2 , no. 9 , September 1, 2010, ISSN  1943-0264 , p. a000703 – a000703 , doi : 10.1101 / cshperspect.a000703 , PMID 20610547 , PMC 2926751 (free full text) - (English, cshlp.org [accessed September 17, 2019]).
  8. ↑ a b c d e f Valentina Casa, Davide Gabellini: A repetitive elements perspective in Polycomb epigenetics . In: Frontiers in Genetics . tape 3 , 2012, ISSN  1664-8021 , doi : 10.3389 / fgene.2012.00199 , PMID 23060903 , PMC 3465993 (free full text) - (English, frontiersin.org [accessed September 17, 2019]).
  9. ↑ a b Hua-Bing Li, Katsuhito Ohno, Hongxing Gui, Vincenzo Pirrotta: Insulators Target Active Genes to Transcription Factories and Polycomb-Repressed Genes to Polycomb Bodies . In: PLoS Genetics . tape 9 , no. 4 , April 18, 2013, ISSN  1553-7404 , p. e1003436 , doi : 10.1371 / journal.pgen.1003436 , PMID 23637616 , PMC 3630138 (free full text) - (English, plos.org [accessed on September 17, 2019]).
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  12. ↑ a b c d e f g h i j k l m J. ŠMIGOVÁ, P. JUDA, J. KREJČÍ, I. RAŠKA: Structural Basis of Polycomb Bodies. (PDF) June 27, 2014, accessed on September 17, 2019 .
  13. ↑ a b c d Moritz Bauer, Johanna Trupke, Leonie Ringrose: The quest for mammalian Polycomb response elements: are we there yet? In: Chromosoma . tape 125 , no. 3 , June 2016, ISSN  0009-5915 , p. 471–496 , doi : 10.1007 / s00412-015-0539-4 , PMID 26453572 , PMC 4901126 (free full text) - (English, springer.com [accessed September 17, 2019]).
  14. ↑ a b c Sandip De, Apratim Mitra, Yuzhong Cheng, Karl Pfeifer, Judith A. Kassis: Formation of a Polycomb Domain in the Absence of Strong Polycomb Response Elements . In: PLOS Genetics . tape 12 , no. 7 , July 28, 2016, ISSN  1553-7404 , p. e1006200 , doi : 10.1371 / journal.pgen.1006200 , PMID 27466807 , PMC 4965088 (free full text) - (English, plos.org [accessed on September 17, 2019]).
  15. ↑ Alaguraj Veluchamy, Teddy Jégu, Federico Ariel, David Latrasse, Kiruthiga Gayathri Mariappan: LHP1 Regulates H3K27me3 Spreading and Shapes the Three-Dimensional Conformation of the Arabidopsis Genome . In: PLoS ONE . tape 11 , no. 7 , July 13, 2016, ISSN  1932-6203 , doi : 10.1371 / journal.pone.0158936 , PMID 27410265 , PMC 4943711 (free full text) - (English).
  16. ↑ a b c d Yuntao S. Mao, Bin Zhang, David L. Spector: Biogenesis and Function of Nuclear Bodies . In: Trends in genetics (TIG) . tape 27 , no. 8 , August 2011, ISSN  0168-9525 , p. 295–306 , doi : 10.1016 / j.tig.2011.05.006 , PMID 21680045 , PMC 3144265 (free full text) - (English).
  17. ↑ M. Carmo-Fonseca, MT Berciano, M. Lafarga: Orphan Nuclear Bodies . In: Cold Spring Harbor Perspectives in Biology . tape 2 , no. 9 , September 1, 2010, ISSN  1943-0264 , p. a000703 – a000703 , doi : 10.1101 / cshperspect.a000703 , PMID 20610547 , PMC 2926751 (free full text) - (English, cshlp.org [accessed September 20, 2019]).
  18. ^ MJ MacPherson, LG Beatty, W. Zhou, M. Du, PD Sadowski: The CTCF Insulator Protein Is Posttranslationally Modified by SUMO . In: Molecular and Cellular Biology . tape 29 , no. 3 , February 1, 2009, ISSN  0270-7306 , p. 714–725 , doi : 10.1128 / MCB.00825-08 , PMID 19029252 , PMC 2630690 (free full text) - (English, asm.org [accessed September 20, 2019]).
  19. ^ Christophe Lavelle, Jean-Marc Victor: Nuclear architecture and dynamics . Elsevier, London 2018, ISBN 978-0-12-803503-0 (English).
  20. ↑ F. Bantignies: Inheritance of Polycomb-dependent chromosomal interactions in Drosophila . In: Genes & Development . tape 17 , no. 19 , October 1, 2003, ISSN  0890-9369 , p. 2406–2420 , doi : 10.1101 / gad.269503 , PMID 14522946 , PMC 218078 (free full text) - (English, genesdev.org [accessed September 20, 2019]).
  21. ↑ Stefanie Rosa, Filomena De Lucia, Joshua S. Mylne, Danling Zhu, Nobuko Ohmido: Physical clustering of FLC alleles during Polycomb-mediated epigenetic silencing in vernalization . In: Genes & Development . tape 27 , no. 17 , September 1, 2013, ISSN  0890-9369 , p. 1845–1850 , doi : 10.1101 / gad.221713.113 , PMID 24013499 , PMC 3778238 (free full text) - (English).
This version was added to the list of articles worth reading on March 27, 2020 .