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. In human embryonic stem cells, the histone demethylase LSD1 is found to occupy the promoters of a subset of developmental genes that bear methylation marks on the lysine residues 4 and 27 of histone 3, and are co-occupied by OCT4 and NANOG. LSD1 participates in the silencing of these genes by controlling the levels of methylation at their regulatory regions on lysine 4 of histone 3.

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Adamo, A., Sesé, B., Boue, S. et al. LSD1 regulates the balance between self-renewal and differentiation in human embryonic stem cells. Nat Cell Biol 13, 652–659 (2011). https://doi.org/10.1038/ncb2246

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