Organizational principles of 3D genome architecture

• Type of Material: Article
• Authors: M.Jordan Rowley, Emory University; Victor Corces, Emory University
• Language: English
• Date: 2018-12-01
• Publisher: Nature Research (part of Springer Nature): Review Journals
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018, Springer Nature Limited.
• Final Published Version (URL): http://dx.doi.org/10.1038/s41576-018-0060-8
• Title of Journal or Parent Work: Nature Reviews Genetics
• ISSN: 1471-0056
• Volume: 19
• Issue: 12
• Start Page: 789
• End Page: 800
• Grant/Funding Information: Work in the authors’ lab is supported by U.S. Public Health Service Award R01 GM035463 (V.G.C.); and Pathway to Independence Award K99/R00 GM127671 (M.J.R.) from the National Institutes of Health.
• Keywords: INSULATED NEIGHBORHOODS; CHROMATIN ARCHITECTURE; PHASE-SEPARATION; Life Sciences & Biomedicine; BINDING; CTCF; MAMMALIAN GENOMES; DOMAINS; Science & Technology; LOOP EXTRUSION; Genetics & Heredity; COHESIN; TRANSCRIPTION
• Research Categories: Biology, Genetics; Biology, General

Abstract

Studies of 3D chromatin organization have suggested that chromosomes are hierarchically organized into large compartments composed of smaller domains called topologically associating domains (TADs). Recent evidence suggests that compartments are smaller than previously thought and that the transcriptional or chromatin state is responsible for interactions leading to the formation of small compartmental domains in all organisms. In vertebrates, CTCF forms loop domains, probably via an extrusion process involving cohesin. CTCF loops cooperate with compartmental domains to establish the 3D organization of the genome. The continuous extrusion of the chromatin fibre by cohesin may also be responsible for the establishment of enhancer–promoter interactions and stochastic aspects of the transcription process. These observations suggest that the 3D organization of the genome is an emergent property of chromatin and its components, and thus may not be only a determinant but also a consequence of its function.