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

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

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Center of Regenerative Medicine in Barcelona, Dr. Aiguader, 88, 08003 Barcelona, Spain.


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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