Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells

Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):996-1001. doi: 10.1073/pnas.1317788111. Epub 2013 Dec 13.

Abstract

Recent studies of genome-wide chromatin interactions have revealed that the human genome is partitioned into many self-associating topological domains. The boundary sequences between domains are enriched for binding sites of CTCC-binding factor (CTCF) and the cohesin complex, implicating these two factors in the establishment or maintenance of topological domains. To determine the role of cohesin and CTCF in higher-order chromatin architecture in human cells, we depleted the cohesin complex or CTCF and examined the consequences of loss of these factors on higher-order chromatin organization, as well as the transcriptome. We observed a general loss of local chromatin interactions upon disruption of cohesin, but the topological domains remain intact. However, we found that depletion of CTCF not only reduced intradomain interactions but also increased interdomain interactions. Furthermore, distinct groups of genes become misregulated upon depletion of cohesin and CTCF. Taken together, these observations suggest that CTCF and cohesin contribute differentially to chromatin organization and gene regulation.

Keywords: 4C; HOX cluster; Hi-C; transcriptional regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • CCCTC-Binding Factor
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Cell Nucleus / metabolism
  • Chromatin / chemistry*
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA-Binding Proteins
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • HEK293 Cells
  • Homeodomain Proteins / metabolism
  • Humans
  • Mitosis
  • Multigene Family
  • Nuclear Proteins / metabolism
  • Phosphoproteins / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Repressor Proteins / metabolism*
  • Transcriptome

Substances

  • CCCTC-Binding Factor
  • CTCF protein, human
  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • RAD21 protein, human
  • Repressor Proteins
  • cohesins

Associated data

  • GEO/GSE44267