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

Antonio Adamo, Borja Sesé, Stephanie Boue, Julio Castaño, Ida Paramonov, Maria J. Barrero, Juan Carlos Izpisua Belmonte

Research output: Contribution to journalArticlepeer-review

260 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)652-661
Number of pages10
JournalNature Cell Biology
Volume13
Issue number6
DOIs
StatePublished - Jun 2011
Externally publishedYes

Bibliographical note

Funding Information:
We thank S. Malik and I. Martinez for critical reading of the manuscript, D. Trono for plasmids pLVTHM and psPAX2, T. Pratt for plasmid pTP6, A. Consiglio for assistance with viral preparations and infection, R. Vassena, I. Rodriguez and A. Sanchez for help with the differentiation experiments, B. Christen for advice on cell treatments and V. Astro for assistance with movie preparation. M.J.B. was partially supported by the Ramón y Cajal programme. B.S. is a predoctoral fellow from the Ministerio de Ciencia e Innovación of Spain. This work was partially supported by grants RYC-2007-01510 and SAF2009-08588 from the Ministerio de Ciencia e Innovación of Spain to M.J.B. and grants from the G. Harold and Leila Y. Mathers Charitable Foundation, Sanofi-Aventis, MICINN, CIBER and Fundacion Cellex to J.C.I.B.

ASJC Scopus subject areas

  • Cell Biology

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