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| Status |
Public on Mar 07, 2018 |
| Title |
NCoR/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming [ChIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Changing the somatic cell transcriptome to a pluripotent state using exogenous reprogramming factors needs transcriptional co-regulators that help activate or suppress gene expression and rewrite the epigenome. Here, we show that reprogramming-specific engagement of the NCoR/SMRT co-repressor complex at key pluripotency loci creates an epigenetic block to reprogramming. HDAC3 executes the repressive function of NCoR/SMRT in reprogramming by inducing histone deacetylation at these loci. Recruitment of NCoR/SMRT-HDAC3 to pluripotency genes is facilitated by all 4 Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) but mostly by c-MYC. Class IIa HDACs further potentiate this recruitment by interacting with both the reprogramming factors and NCoR/SMRT. Consequently, depleting NCoR/SMRT-HDAC3 function enables high efficiency of reprogramming, while elevating NCoR/SMRT-HDAC3 recruitment at pluripotency loci by over-expressing constitutively active class IIa HDACs derails it. Our findings thus uncover an unexpected epigenetic mechanism involving c-MYC, whose manipulation greatly enhances reprogramming efficiency.
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| Overall design |
ChIP-seq data consisting of NCoR or SMRT binding in ESCs, OSKM-transfected MEFs (Day 9) and H3K27ac ChIP-seq in OSKM-transfected MEFs (Day 5, 9 and 13) either co-transfected with a FLAG control or a HDAC3-Y298F deacetylase null mutant
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| |
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| Contributor(s) |
Hutchins AP, Esteban MA, Zhuang Q |
| Citation(s) |
29531310 |
| |
| Submission date |
Jul 10, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Andrew P Hutchins |
| E-mail(s) |
andrewh@sustech.edu.cn
|
| Organization name |
Southern University of Science and Technology
|
| Department |
Bioinformatics
|
| Lab |
Bioinformatics and Genomics
|
| Street address |
1088 Xueyuan Rd
|
| City |
Shenzhen |
| ZIP/Postal code |
518055 |
| Country |
China |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (13)
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| This SubSeries is part of SuperSeries: |
| GSE70740 |
NCoR/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming |
|
| Relations |
| BioProject |
PRJNA289461 |
| SRA |
SRP060656 |
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