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

被引:251
作者
Adamo, Antonio [1 ]
Sese, Borja [1 ]
Boue, Stephanie [1 ]
Castano, Julio [1 ]
Paramonov, Ida [1 ]
Barrero, Maria J. [1 ]
Izpisua Belmonte, Juan Carlos [1 ,2 ]
机构
[1] Ctr Regenerat Med Barcelona, Barcelona 08003, Spain
[2] Salk Inst Biol Studies, La Jolla, CA 92037 USA
关键词
PROTEIN-INTERACTION NETWORK; DEVELOPMENTAL REGULATORS; TRANSCRIPTION; PROMOTES; GENES; RNA; DEMETHYLATION; METHYLATION; EXPRESSION; REPRESSION;
D O I
10.1038/ncb2246
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We identify LSD1 (lysine-specific demethylase 1; also known as KDM1A and A0F2) 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.
引用
收藏
页码:652 / U265
页数:20
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