4.5 Review

How DNA loop extrusion mediated by cohesin enables V(D)J recombination

期刊

CURRENT OPINION IN CELL BIOLOGY
卷 70, 期 -, 页码 75-83

出版社

CURRENT BIOLOGY LTD
DOI: 10.1016/j.ceb.2020.11.007

关键词

Chromatin looping; Cohesin; CTCF; Locus contraction; Loop extrusion; V(D)J recombination; Topologically associating domains; Wapl

资金

  1. Boehringer Ingelheim
  2. Austrian Research Promotion Agency [FFG-852936]
  3. European Research Council under the European Union [693949]
  4. Human Frontier Science Program [RGP0057/2018]
  5. Vienna Science and Technology Fund [LS19-029]
  6. European Research Council (ERC) [693949] Funding Source: European Research Council (ERC)

向作者/读者索取更多资源

Structural maintenance of chromosomes' complexes play a crucial role in folding genomic DNA into loops, especially in V(D)J recombination of antigen receptor genes in B and T cells. Regulating the formation and recombination of chromatin loops ensures the diversity of B-cell receptors and antibodies.
Structural maintenance of chromosomes' (SMC) complexes are required for the folding of genomic DNA into loops. Theoretical considerations and single-molecule experiments performed with the SMC complexes cohesin and condensin indicate that DNA folding occurs via loop extrusion. Recent work indicates that this process is essential for the assembly of antigen receptor genes by V(D)J recombination in developing B and T cells of the vertebrate immune system. Here, I review how recent studies of the mouse immunoglobulin heavy chain locus Igh have provided evidence for this hypothesis and how the formation of chromatin loops by cohesin and regulation of this process by CTCF and Wapl might ensure that all variable gene segments in this locus (V-H segments) participate in recombination with a re-arranged DJ(H) segment, to ensure generation of a maximally diverse repertoire of B-cell receptors and antibodies.

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