LSD1 Regulates the Balance Between Self-Renewal and Differentiation in Human Embryonic Stem Cells

Nat Cell Biol. 2011 Jun;13(6):652-9. doi: 10.1038/ncb2246. Epub 2011 May 22.

Abstract

We identify LSD1 (lysine-specific demethylase 1; also known as KDM1A and AOF2) as a key histone modifier that participates in the maintenance of pluripotency through the regulation of bivalent domains, a chromatin environment present at the regulatory regions of developmental genes that contains both H3K4 di/trimethylation and H3K27 trimethylation marks. LSD1 occupies the promoters of a subset of developmental genes that contain bivalent domains and are co-occupied by OCT4 and NANOG in human embryonic stem cells, where it controls the levels of H3K4 methylation through its demethylase activity. Thus, LSD1 has a role in maintaining the silencing of several developmental genes in human embryonic stem cells by regulating the critical balance between H3K4 and H3K27 methylation at their regulatory regions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Bone Morphogenetic Protein 2 / metabolism
  • Cell Cycle
  • Cell Differentiation*
  • Cell Line
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism*
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Histone Demethylases / genetics
  • Histone Demethylases / metabolism*
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / metabolism
  • Methylation
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Histone Demethylases
  • Jumonji Domain-Containing Histone Demethylases
  • KDM1A protein, human
  • Kdm6b protein, mouse