NCoR/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming.
Nat Cell Biol
; 20(4): 400-412, 2018 04.
Article
in En
| MEDLINE
| ID: mdl-29531310
ABSTRACT
Somatic cell reprogramming by exogenous factors requires cooperation with transcriptional co-activators and co-repressors to effectively remodel the epigenetic environment. How this interplay is regulated remains poorly understood. Here, we demonstrate that NCoR/SMRT co-repressors bind to pluripotency loci to create a barrier to reprogramming with the four Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC), and consequently, suppressing NCoR/SMRT significantly enhances reprogramming efficiency and kinetics. The core epigenetic subunit of the NCoR/SMRT complex, histone deacetylase 3 (HDAC3), contributes to the effects of NCoR/SMRT by inducing histone deacetylation at pluripotency loci. Among the Yamanaka factors, recruitment of NCoR/SMRT-HDAC3 to genomic loci is mostly facilitated by c-MYC. Hence, we describe how c-MYC is beneficial for the early phase of reprogramming but deleterious later. Overall, we uncover a role for NCoR/SMRT co-repressors in reprogramming and propose a dual function for c-MYC in this process.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proto-Oncogene Proteins c-myc
/
Pluripotent Stem Cells
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Epigenesis, Genetic
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Cellular Reprogramming
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Nuclear Receptor Co-Repressor 1
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Nuclear Receptor Co-Repressor 2
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Mouse Embryonic Stem Cells
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Cell Biol
Year:
2018
Document type:
Article
Affiliation country: