دورية أكاديمية
Interplay between CTCF boundaries and a super enhancer controls cohesin extrusion trajectories and gene expression.
| العنوان: | Interplay between CTCF boundaries and a super enhancer controls cohesin extrusion trajectories and gene expression. |
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| المؤلفون: | Vos ESM; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands., Valdes-Quezada C; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands., Huang Y; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands., Allahyar A; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands., Verstegen MJAM; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands., Felder AK; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands., van der Vegt F; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands., Uijttewaal ECH; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands., Krijger PHL; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands., de Laat W; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands. Electronic address: w.delaat@hubrecht.eu. |
| المصدر: | Molecular cell [Mol Cell] 2021 Aug 05; Vol. 81 (15), pp. 3082-3095.e6. Date of Electronic Publication: 2021 Jun 30. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 9802571 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4164 (Electronic) Linking ISSN: 10972765 NLM ISO Abbreviation: Mol Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge Ma : Cell Press Original Publication: Cambridge, Mass. : Cell Press, c1997- |
| مواضيع طبية MeSH: | Enhancer Elements, Genetic*, CCCTC-Binding Factor/*metabolism , Chromatin/*genetics, Animals ; CCCTC-Binding Factor/genetics ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Chromatin/metabolism ; Chromosomal Proteins, Non-Histone/genetics ; Chromosomal Proteins, Non-Histone/metabolism ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Gene Expression ; Mice ; Mouse Embryonic Stem Cells ; Nuclear Receptor Coactivator 2/genetics ; Promoter Regions, Genetic ; RNA-Binding Proteins/genetics ; Transcription Factors/genetics ; Cohesins |
| مستخلص: | To understand how chromatin domains coordinate gene expression, we dissected select genetic elements organizing topology and transcription around the Prdm14 super enhancer in mouse embryonic stem cells. Taking advantage of allelic polymorphisms, we developed methods to sensitively analyze changes in chromatin topology, gene expression, and protein recruitment. We show that enhancer insulation does not rely strictly on loop formation between its flanking boundaries, that the enhancer activates the Slco5a1 gene beyond its prominent domain boundary, and that it recruits cohesin for loop extrusion. Upon boundary inversion, we find that oppositely oriented CTCF terminates extrusion trajectories but does not stall cohesin, while deleted or mutated CTCF sites allow cohesin to extend its trajectory. Enhancer-mediated gene activation occurs independent of paused loop extrusion near the gene promoter. We expand upon the loop extrusion model to propose that cohesin loading and extrusion trajectories originating at an enhancer contribute to gene activation. Competing Interests: Declaration of interests W.d.L. is a founder and shareholder of Cergentis BV. (Copyright © 2021 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: CTCF; TADs; chromatin; cohesin; domains; enhancers; gene regulation; genome organization; loop extrusion; loops |
| المشرفين على المادة: | 0 (CCCTC-Binding Factor) 0 (CTCF protein, human) 0 (Cell Cycle Proteins) 0 (Chromatin) 0 (Chromosomal Proteins, Non-Histone) 0 (DNA-Binding Proteins) 0 (Ncoa2 protein, mouse) 0 (Nuclear Receptor Coactivator 2) 0 (Prdm14 protein, mouse) 0 (RNA-Binding Proteins) 0 (Rad21 protein, mouse) 0 (Transcription Factors) |
| تواريخ الأحداث: | Date Created: 20210701 Date Completed: 20210825 Latest Revision: 20231213 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.molcel.2021.06.008 |
| PMID: | 34197738 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1097-4164 |
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| DOI: | 10.1016/j.molcel.2021.06.008 |