Topological Domains in Mammalian Genomes Identified by Analysis of Chromatin Interactions

Details

• Alternative Title:
  Nature
• Personal Author:
  Dixon, Jesse R. ; Selvaraj, Siddarth ; Yue, Feng ; Kim, Audrey ; Li, Yan ; Shen, Yin ; Hu, Ming ; Liu, Jun S. ; Ren, Bing
• Description:
  The spatial organization of the genome is intimately linked to its biological function, yet our understanding of higher order genomic structure is coarse, fragmented and incomplete. In the nucleus of eukaryotic cells, interphase chromosomes occupy distinct chromosome territories, and numerous models have been proposed for how chromosomes fold within chromosome territories. These models, however, provide only few mechanistic details about the relationship between higher order chromatin structure and genome function. Recent advances in genomic technologies have led to rapid advances in the study of three-dimensional genome organization. In particular, Hi-C has been introduced as a method for identifying higher order chromatin interactions genome wide. Here we investigate the three-dimensional organization of the human and mouse genomes in embryonic stem cells and terminally differentiated cell types at unprecedented resolution. We identify large, megabase-sized local chromatin interaction domains, which we term 'topological domains', as a pervasive structural feature of the genome organization. These domains correlate with regions of the genome that constrain the spread of heterochromatin. The domains are stable across different cell types and highly conserved across species, indicating that topological domains are an inherent property of mammalian genomes. Finally, we find that the boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome.
• Subjects:
  Animals Binding Sites Cell Differentiation Chromatin Chromosomes Embryonic Stem Cells Evolution, Molecular Female Genes, Essential Genome Heterochromatin Humans Male Mammals Mice Repressor Proteins RNA, Transfer Short Interspersed Nucleotide Elements

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• Source:
  Nature. 485(7398):376-380.
• Pubmed ID:
  22495300
• Pubmed Central ID:
  PMC3356448
• Document Type:
  Journal Article
• Funding:
  R01 HG003991/HG/NHGRI NIH HHS/United States ; R01 HG003991-03/HG/NHGRI NIH HHS/United States ; R01 HG003991-03S1/HG/NHGRI NIH HHS/United States ; R01GH003991/GH/CGH CDC HHS/United States
• Volume:
  485
• Issue:
  7398
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:7547c5e744d44f0403978f5b911ca8ecf4678705321115bb2e6bcfc8b07e1ef8
• Download URL:
  https://stacks.cdc.gov/view/cdc/22685/cdc_22685_DS1.pdf
• File Type:
  [PDF - 1.15 MB ]