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LSD1 regulates the balance between self-renewal and differentiation in human embryonic stem cells.

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.

Pubmed ID: 21602794

Authors

  • Adamo A
  • Sesé B
  • Boue S
  • Castaño J
  • Paramonov I
  • Barrero MJ
  • Izpisua Belmonte JC

Journal

Nature cell biology

Publication Data

June 2, 2011

Associated Grants

None

Mesh Terms

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