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Binding of HMGN proteins to cell specific enhancers stabilizes cell identity.


ABSTRACT: The dynamic nature of the chromatin epigenetic landscape plays a key role in the establishment and maintenance of cell identity, yet the factors that affect the dynamics of the epigenome are not fully known. Here we find that the ubiquitous nucleosome binding proteins HMGN1 and HMGN2 preferentially colocalize with epigenetic marks of active chromatin, and with cell-type specific enhancers. Loss of HMGNs enhances the rate of OSKM induced reprogramming of mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs), and the ASCL1 induced conversion of fibroblast into neurons. During transcription factor induced reprogramming to pluripotency, loss of HMGNs accelerates the erasure of the MEF-specific epigenetic landscape and the establishment of an iPSCs-specific chromatin landscape, without affecting the pluripotency potential and the differentiation potential of the reprogrammed cells. Thus, HMGN proteins modulate the plasticity of the chromatin epigenetic landscape thereby stabilizing, rather than determining cell identity.

SUBMITTER: He B 

PROVIDER: S-EPMC6286339 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Binding of HMGN proteins to cell specific enhancers stabilizes cell identity.

He Bing B   Deng Tao T   Zhu Iris I   Furusawa Takashi T   Zhang Shaofei S   Tang Wei W   Postnikov Yuri Y   Ambs Stefan S   Li Caiyi Cherry CC   Livak Ferenc F   Landsman David D   Bustin Michael M  

Nature communications 20181207 1


The dynamic nature of the chromatin epigenetic landscape plays a key role in the establishment and maintenance of cell identity, yet the factors that affect the dynamics of the epigenome are not fully known. Here we find that the ubiquitous nucleosome binding proteins HMGN1 and HMGN2 preferentially colocalize with epigenetic marks of active chromatin, and with cell-type specific enhancers. Loss of HMGNs enhances the rate of OSKM induced reprogramming of mouse embryonic fibroblasts (MEFs) into in  ...[more]

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