HDAC1 regulates pluripotency and lineage specific transcriptional networks in embryonic and trophoblast stem cells

Nucleic Acids Res. 2012 Apr;40(7):2925-39. doi: 10.1093/nar/gkr1151. Epub 2011 Dec 10.


Epigenetic regulation of gene expression is important in maintaining self-renewal of embryonic stem (ES) and trophoblast stem (TS) cells. Histone deacetylases (HDACs) negatively control histone acetylation by removing covalent acetylation marks from histone tails. Because histone acetylation is a known mark for active transcription, HDACs presumably associate with inactive genes. Here, we used genome-wide chromatin immunoprecipitation to investigate targets of HDAC1 in ES and TS cells. Through evaluation of genes associated with acetylated histone H3 marks, and global expression analysis of Hdac1 knockout ES and trichostatin A-treated ES and TS cells, we found that HDAC1 occupies mainly active genes, including important regulators of ES and TS cells self-renewal. We also observed occupancy of methyl-CpG binding domain protein 3 (MBD3), a subunit of the nucleosome remodeling and histone deacetylation (NuRD) complex, at a subset of HDAC1-occupied sequences in ES cells, including the pluripotency regulators Oct4, Nanog and Kfl4. By mapping HDAC1 targets on a global scale, our results describe further insight into epigenetic mechanisms of ES and TS cells self-renewal.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylation
  • Animals
  • Cell Lineage
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism
  • Embryonic Stem Cells / enzymology
  • Embryonic Stem Cells / metabolism*
  • Gene Regulatory Networks*
  • Histone Deacetylase 1 / metabolism*
  • Histones / metabolism
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / metabolism
  • Mice
  • Pluripotent Stem Cells / enzymology
  • Pluripotent Stem Cells / metabolism*
  • Trophoblasts / cytology
  • Trophoblasts / enzymology
  • Trophoblasts / metabolism*


  • DNA-Binding Proteins
  • Histones
  • Histone Deacetylase 1
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex

Associated data

  • GEO/GSE26087