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

doi:10.1038/ncb2246

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 journal › Article › peer-review

240 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 language	English (US)
Pages (from-to)	652-661
Number of pages	10
Journal	Nature Cell Biology
Volume	13
Issue number	6
DOIs	https://doi.org/10.1038/ncb2246
State	Published - Jun 1 2011
Externally published	Yes

ASJC Scopus subject areas

Cell Biology

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title = "LSD1 regulates the balance between self-renewal and differentiation in human embryonic stem cells",

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.",

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AU - Adamo, Antonio

AU - Sesé, Borja

AU - Boue, Stephanie

AU - Castaño, Julio

AU - Paramonov, Ida

AU - Barrero, Maria J.

AU - Izpisua Belmonte, Juan Carlos

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AB - 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.

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

Abstract

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