Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes

Cell. 2014 Oct 9;159(2):374-387. doi: 10.1016/j.cell.2014.09.030.

Abstract

The pluripotent state of embryonic stem cells (ESCs) is produced by active transcription of genes that control cell identity and repression of genes encoding lineage-specifying developmental regulators. Here, we use ESC cohesin ChIA-PET data to identify the local chromosomal structures at both active and repressed genes across the genome. The results produce a map of enhancer-promoter interactions and reveal that super-enhancer-driven genes generally occur within chromosome structures that are formed by the looping of two interacting CTCF sites co-occupied by cohesin. These looped structures form insulated neighborhoods whose integrity is important for proper expression of local genes. We also find that repressed genes encoding lineage-specifying developmental regulators occur within insulated neighborhoods. These results provide insights into the relationship between transcriptional control of cell identity genes and control of local chromosome structure.

Publication types

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

MeSH terms

  • Animals
  • CCCTC-Binding Factor
  • Cell Cycle Proteins / metabolism
  • Chromatin Immunoprecipitation
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosomes, Mammalian / metabolism*
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Genome
  • High-Throughput Nucleotide Sequencing
  • Mice
  • Organ Specificity
  • Pluripotent Stem Cells / metabolism
  • Repressor Proteins / metabolism
  • Sequence Analysis, DNA

Substances

  • CCCTC-Binding Factor
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Ctcf protein, mouse
  • Repressor Proteins
  • cohesins

Associated data

  • GEO/GSE57913