RAD21 cooperates with pluripotency transcription factors in the maintenance of embryonic stem cell identity

PLoS One. 2011 May 12;6(5):e19470. doi: 10.1371/journal.pone.0019470.

Abstract

For self-renewal, embryonic stem cells (ESCs) require the expression of specific transcription factors accompanied by a particular chromosome organization to maintain a balance between pluripotency and the capacity for rapid differentiation. However, how transcriptional regulation is linked to chromosome organization in ESCs is not well understood. Here we show that the cohesin component RAD21 exhibits a functional role in maintaining ESC identity through association with the pluripotency transcriptional network. ChIP-seq analyses of RAD21 reveal an ESC specific cohesin binding pattern that is characterized by CTCF independent co-localization of cohesin with pluripotency related transcription factors Oct4, Nanog, Sox2, Esrrb and Klf4. Upon ESC differentiation, most of these binding sites disappear and instead new CTCF independent RAD21 binding sites emerge, which are enriched for binding sites of transcription factors implicated in early differentiation. Furthermore, knock-down of RAD21 causes expression changes that are similar to expression changes after Nanog depletion, demonstrating the functional relevance of the RAD21--pluripotency transcriptional network association. Finally, we show that Nanog physically interacts with the cohesin or cohesin interacting proteins STAG1 and WAPL further substantiating this association. Based on these findings we propose that a dynamic placement of cohesin by pluripotency transcription factors contributes to a chromosome organization supporting the ESC expression program.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cell Cycle Proteins / physiology
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • Chromosomal Proteins, Non-Histone / physiology
  • Embryonic Stem Cells / cytology*
  • Gene Expression Profiling
  • Homeodomain Proteins / physiology
  • Mice
  • Nanog Homeobox Protein
  • Nuclear Proteins / physiology*
  • Phosphoproteins / physiology*
  • Pluripotent Stem Cells / cytology*
  • Transcription Factors / physiology*

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Homeodomain Proteins
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • Nuclear Proteins
  • Phosphoproteins
  • Rad21 protein, mouse
  • Transcription Factors
  • cohesins

Associated data

  • GEO/GSE24030