Core framework / core matrix attachment regions

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SMAR functions: constitutive and facultative. A chromatin domain with constitutive S / MARs at the end (I). When the functional circumstances require a specific translocation of the constitutive gene to attach to the matrix, the S / MARs respond to the changes that are initiated by transcription factors (TF) and supported by histone acetylation . The totality of the changes are those that pull the gene through the transcriptional "machinery" (II). The transcription has ended (III), this is followed by the dissociation of the transcription complex (IV).

The term Kerngerüst- / Kernmatrixanheftungsregionen (engl. Scaffold / matrix attachment region , S / MAR), and scaffold attachment region (SAR) or matrix-associated element (MAR), called describes DNA sequences of eukaryotic chromosomes or 30- nm fiber or the chromatin to which the nuclear matrix attaches. S / MARs can be described as architectural DNA components that have an organizational influence on the genome as well as the activation and inactivation of the eukaryotic genome segment and also mediate the structural organization, i.e. H. the condensation of chromatin within the nucleus. These elements form anchor points of the DNA for the chromate structure and serve to arrange the chromatin in structural domains. Studies of individual genes led to the conclusion that the complex and dynamic organization of chromatin mediated by S / MARs plays an important role in the regulation of gene expression .

overview

It has been known for many years that a polymeric network, a so-called nuclear matrix or core framework, is an essential component of eukaryotic cell nuclei . The nuclear skeleton acts as a dynamic support for numerous specific events related to the transcription of the genetic information being propagated.

S / MARs do not record any cartographically random sections in the genome. They occur on the sides of transcribed regions in 5 ' introns and Genbruchpunkt cluster regions - on (gene breakpoint cluster regions BCRs). As connection points for common core structural proteins (e.g. the lamines of the lamina or matrine such as ARBP / meCP2, HMG 1 , HMG 2, nucleolin or histones ), S / MARs are required for authentic and efficient replication , transcription , recombination and condensation of the Chromosomes . S / MARs do not have an obvious consensus sequence . Although primitive elements are made up of several hundred AT-rich base pairs in lengths , the overall composition is definitely not the primary variable governing their activity. Instead, their function requires a pattern of AT areas that enables local strand separation under torsional stresses . The anchor points or contact points are mediated by MAR proteins. These sites in the DNA are 100 to 1000 base pairs in length and have an AT content of 70%. In addition, due to the AT base pairing, they are slightly bent with only two hydrogen bonds , so that the connection between the DNA and the matrix is ​​supported.

Bioinformatic approaches support the thesis that S / MARs not only separate a certain transcriptional unit (chromatin domain or DNA segment that is condensed by means of nucleosomes ) from its neighbors, but also offer platforms for the precipitation of factors, the transcriptional reactions within a given domain enable. The increased tendency to separate the DNA strands (the so-called: 'stress induced duplex destabilization' potential, SIDD) can lead to the formation of secondary structures such as B. cruciforms or hatching structures are used, which are decisive characteristics for a group of enzymes ( DNAsen , topoisomerase , poly (ADP-ribosyl) polymerase and enzymes of the histone acetylation and DNA methylation complex). S / MARs have been categorized either as constitutive (acting as permanent domain delimitation in all cell types) or as facultative (cell type or function related), depending on their dynamic properties.

While the number of S / MARs in the human genome was estimated at 64,000 (chromatin domains) plus an additional 10,000 (replication foci), in 2007 only a small fraction (559 for all eukaryotes) still had the norm for the criteria for annotation in the S / MARt databases met.

Condition-dependent properties of S / MARs

Current views of the nuclear matrix describe it as a dynamic object that adapts its properties to the corresponding requirements of the cell nucleus - just like the cytoskeleton , it adapts its structure and function to external signals . In retrospect, two approaches are important in the discovery of S / MARs:

  • the description of the SARs (scaffold-attachment elements) from Laemmli & Co., which were believed to delimit a given chromatin domain
  • the immunoglobulin kappa chain enhancer characterization of MARs (matrix-associated regions) the first examples, depending on its occupation with transcription factors support

Subsequent work has demonstrated that both functions of the elements - the constitutive (SAR-like) and the facultative (MAR-like) - are dependent on the context. Whereas constitutive S / MARs were found in all cell types associated with DNAse I hypersensitive sites (regardless of whether the adjacent domain was transcribed or not), the DNAse I hypersensitivity of the facultative type depends on the transcription status. The most striking difference between these two functional types of S / MARs is their size: the constitutive elements are likely to extend over several kbp, whereas the optional ones are the smaller ones, around 300 bp.

The figure shows the current understanding of these properties and contains the following findings:

  • the dynamic properties of the S / MAR-scaffold contacts, derived from research using haloFISH (halo- fluorescence-in-situ-hybridization )
  • the fact that during transcription, DNA is spooled by RNA polymerase , which in turn is a solid component of the nuclear matrix
  • the fact that certain domain-intrinsic S / MARs require the support of an adjacent transcription factor in order to become active

Continuing

In Arabidopsis thaliana, Tetko established a relationship between intragenic S / MARs and spatiotemporal gene expression (location and time specific expression related to tissue regions within an organism during development). Patterns containing S / MARs were found on a gene map that emphasizes tissue and organ-specific gene expression as well as that of development . Above all, the genes of the transcription factors contain a significantly higher amount of S / MARs. The striking difference in the expression characteristics of the genes containing S / MARs underlines the importance of their functional importance and that of the structure-chromosomal characteristics for gene regulation in plants as well as in other eukaryotes .

Individual evidence

  1. ↑ JM Weitzel, H. Buhrmester, WH Strätling: Chicken MAR-binding protein ARBP is homologous to rat methyl-CpG-binding protein MeCP2. In: Molecular and cellular biology. Volume 17, Number 9, September 1997, pp. 5656-5666, PMID 9271441 , PMC 232414 (free full text).
  2. ↑ HMGB2 in the English language Wikipedia
  3. ↑ David P. Clark, Nanette J. Pazdernik: Molecular Biotechnology - Fundamentals and Applications. Spektrum Akad. Verlag, 2009, ISBN 978-3-8274-2128-9 , p. 7.
  4. ↑ SIDD on the English Wikipedia
  5. ↑ SMARtDB
  6. ↑ J. Mirkovitch, ME Mirault, UK Laemmli: Organization of the higher-order chromatin loop: specific DNA attachment sites on nuclear scaffold . In: Cell . tape 39 , no. 1 , November 1984, pp. 223-332 , doi : 10.1016 / 0092-8674 (84) 90208-3 , PMID 6091913 .
  7. ↑ PN Cockerill, WT Garrard: Chromosomal loop anchorage of the kappa immunoglobulin gene occurs next to the enhancer in a region containing topoisomerase II sites . In: Cell . tape 44 , no. 2 , January 1986, pp. 273-82 , doi : 10.1016 / 0092-8674 (86) 90761-0 , PMID 3002631 .
  8. ↑ DNAse I hypersensitive site in the English language Wikipedia
  9. ↑ a b M. Klar, E. Stellamanns, P. Ak, A. Gluch, J. Bode: Dominant genomic structures: detection and potential signal functions in the interferon-beta domain . In: Genes . tape 364 , December 2005, p. 79-89 , doi : 10.1016 / j.gene.2005.07.023 , PMID 16185826 .
  10. ↑ HH Heng, S. Goetze, CJ Ye u. a .: Chromatin loops are selectively anchored using scaffold / matrix-attachment regions . In: J. Cell. Sci. tape 117 , Pt 7, March 2004, p. 999-1008 , doi : 10.1242 / jcs.00976 , PMID 14996931 .
  11. ^ DA Jackson, A. Dolle, G. Robertson, PR Cook: The attachments of chromatin loops to the nucleoskeleton . In: Cell Biol. Int. Rep. Band 16 , no. 8 , August 1992, p. 687-96 , doi : 10.1016 / s0309-1651 (05) 80013-x , PMID 1446346 .
  12. ↑ Igor V. Tetko, Georg Haberer, Stephen Rudd, Blake Meyers, Hans-Werner Mewes, Klaus Mayer FX: Spatiotemporal Expression Control Correlates with intragenic scaffold matrix attachment regions (S / MARs) in Arabidopsis thaliana. In: PLoS Computational Biology. 2 (2006), pp. 136-145. plosjournals.org ( Memento of the original from July 10, 2012 in the web archive archive.today ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. , doi: 10.1371 / journal.pcbi.0020021 . @1@ 2Template: Webachiv / IABot / compbiol.plosjournals.org