Locus control region

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As locus control regions ( English locus control region , LCRs) are sequence segments in the genome of eukaryotes called, who have the ability, the transcription rate increase adjacent genes tissue specific or decrease.

The concept of the locus control regions is based on the observation that the tissue-specific regulation of gene expression, both during development and in adult organisms, is not only based on nearby regulatory elements (such as promoters , enhancers , silencers ), but also on interactions with more distant ones regulatory elements on the same chromosome . LCRs can be many thousands of base pairs away from the start of transcription. They belong to the DNase-I sensitive regions, so it is assumed that they have an 'open' chromatin structure. In LCRs playing Supercoiling or the unwinding of the DNA a role. LCRs can be an essential prerequisite for the transcription of certain genes in certain areas.

In humans, 20 gene families are known, the expression of which is controlled by LCRs. A well-known example is the LCR of the β-globin locus .

Model ideas

There are two models of how LCRs can act on transcription many base pairs away from their location.

The looping model
The LCR sequence of the DNA forms a loop that approximates the gene that is to be transcribed. This loop approaches the binding sites of the transcription machinery (a protein complex ) so closely that the LCR can influence the transcription of this gene.
The spreading model
A signal generated by a regulatory element propagates along the chromatin until it hits a proximal promoter.

history

The LCRs were identified over 20 years ago. In studies on transgenic mice, it was found that the LCR is responsible for the normal regulation of gene expression of beta globulins.

Individual evidence

  1. ^ Q. Li, KR Peterson, X. Fang, G. Stamatoyannopoulos: Locus control regions . In: Blood . tape 100 , no. 9 , November 2002, pp. 3077-3086 , doi : 10.1182 / blood-2002-04-1104 , PMID 12384402 , PMC 2811695 (free full text).
  2. ↑ A. Dean: In the loop: long range chromatin interactions and gene regulation. In: Briefings in functional genomics. 10, No. 1, January 2011, ISSN  2041-2657 , pp. 3–10, doi: 10.1093 / bfgp / elq033 , PMID 21258045 , PMC 3040559 (free full text).
  3. ↑ A. Kim, A. Dean: Chromatin loop formation in the? -Globin locus and its role in globin gene transcription. In: Molecules and cells. 34, No. 1, July 2012, ISSN  0219-1032 , pp. 1–5, doi: 10.1007 / s10059-012-0048-8 , PMID 22610406 , PMC 3887778 (free full text).
  4. ↑ MB Gerstein et al: What is a gene, post-ENCODE? History and updated definition . In: Genome Res. Volume 17 , no. 6 , June 2007, p. 669-681 , doi : 10.1101 / gr.6339607 , PMID 17567988 .