دورية أكاديمية
أعرض في EDS

Building regulatory landscapes reveals that an enhancer can recruit cohesin to create contact domains, engage CTCF sites and activate distant genes.

التفاصيل البيبلوغرافية
العنوان: Building regulatory landscapes reveals that an enhancer can recruit cohesin to create contact domains, engage CTCF sites and activate distant genes.
المؤلفون: Rinzema NJ; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., Sofiadis K; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., Tjalsma SJD; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., Verstegen MJAM; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., Oz Y; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., Valdes-Quezada C; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., Felder AK; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., Filipovska T; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., van der Elst S; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., de Andrade Dos Ramos Z; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., Han R; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., Krijger PHL; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., de Laat W; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands. w.laat@hubrecht.eu.
المصدر: Nature structural & molecular biology [Nat Struct Mol Biol] 2022 Jun; Vol. 29 (6), pp. 563-574. Date of Electronic Publication: 2022 Jun 16.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101186374 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1545-9985 (Electronic) Linking ISSN: 15459985 NLM ISO Abbreviation: Nat Struct Mol Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York : Nature Pub. Group, c2004-
مواضيع طبية MeSH: Cell Cycle Proteins*/genetics , Cell Cycle Proteins*/metabolism , Chromosomal Proteins, Non-Histone*/genetics , Chromosomal Proteins, Non-Histone*/metabolism, Binding Sites ; CCCTC-Binding Factor/genetics ; CCCTC-Binding Factor/metabolism ; Chromatin/genetics ; Enhancer Elements, Genetic/genetics ; Cohesins
مستخلص: Developmental gene expression is often controlled by distal regulatory DNA elements called enhancers. Distant enhancer action is restricted to structural chromosomal domains that are flanked by CTCF-associated boundaries and formed through cohesin chromatin loop extrusion. To better understand how enhancers, genes and CTCF boundaries together form structural domains and control expression, we used a bottom-up approach, building series of active regulatory landscapes in inactive chromatin. We demonstrate here that gene transcription levels and activity over time reduce with increased enhancer distance. The enhancer recruits cohesin to stimulate domain formation and engage flanking CTCF sites in loop formation. It requires cohesin exclusively for the activation of distant genes, not of proximal genes, with nearby CTCF boundaries supporting efficient long-range enhancer action. Our work supports a dual activity model for enhancers: its classic role of stimulating transcription initiation and elongation from target gene promoters and a role of recruiting cohesin for the creation of chromosomal domains, the engagement of CTCF sites in chromatin looping and the activation of distal target genes.
(© 2022. The Author(s).)
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المشرفين على المادة: 0 (CCCTC-Binding Factor)
0 (Cell Cycle Proteins)
0 (Chromatin)
0 (Chromosomal Proteins, Non-Histone)
تواريخ الأحداث: Date Created: 20220617 Date Completed: 20220621 Latest Revision: 20231213
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9205769
DOI: 10.1038/s41594-022-00787-7
PMID: 35710842
قاعدة البيانات: MEDLINE
الوصف
تدمد:1545-9985
DOI:10.1038/s41594-022-00787-7