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The Sin3a/HDAC co-repressor complex cooperates with Nanog in promoting stem cell pluripotency and somatic cell reprogramming

ABSTRACT: The Sin3a/HDAC co-repressor complex cooperates with Nanog in promoting stem cell pluripotency and somatic cell reprogramming

PROVIDER: PRJNA356688 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5087240.fastq.gz	Fastqsanger.gz
	SRR5087250.fastq.gz	Fastqsanger.gz
	SRR5087260.fastq.gz	Fastqsanger.gz
	SRR5087270.fastq.gz	Fastqsanger.gz
	SRR5087241.fastq.gz	Fastqsanger.gz

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The Sin3a/HDAC co-repressor complex cooperates with Nanog in promoting stem cell pluripotency and somatic cell reprogramming [ChIP-Seq]

Project description:Despite the requirement of Sin3a for survival of early embryos and embryonic stem cells (ESCs), mechanistic action of Sin3a in the maintenance and establishment of pluripotency remains unexplored. Here we report the transcriptional regulatory roles of Sin3a in maintaining ESC pluripotency and in reprogramming somatic cells towards full pluripotency. Sin3a/HDAC complex members were enriched in an extended Nanog interactome and exhibited a predominant transcriptional co-activator role at a global level in ESCs. We also established a critical role for Sin3a in efficient reprogramming of somatic cells towards full pluripotency. Nanog and Sin3a co-localize at almost all of their genome-wide targets in pre-iPSCs, and both factors are required to directly induce a synergistic transcriptional program wherein pluripotency genes are activated and reprogramming barrier genes are repressed. Our results, for the first time, establish positive roles of the Sin3a/HDAC complex in the maintenance and establishment of pluripotency.

2017-02-21 | GSE91021 | GEO

The Sin3a/HDAC co-repressor complex cooperates with Nanog in promoting stem cell pluripotency and somatic cell reprogramming [Microarray Expression]

2017-02-21 | GSE90986 | GEO

SIN3A Acetylation Complex - Fam60a defines a variant Sin3a-Hdac complex in embryonic stem cells required for self-renewal

Project description:Sin3a is the central scaffold protein of the prototypical Hdac1/2 chromatin repressor complex, crucially required during early embryonic development for the growth of pluripotent cells of the inner cell mass. Here, we explore the endogenous composition of the Sin3a-Hdac complex in pluripotent embryonic stem (ES) and differentiated cells. To do this, we established an endogenous double immunoprecipitation strategy coupled with quantitative mass spectrometry (ENDIP-MS) allowing us to define the precise composition of the Sin3a complex in multiple cell types. We identify the Fam60a subunit as a key defining feature of a variant Sin3a complex present in ES cells, but not in differentiated cells. Fam60a co-occupies H3K4me3 positive promoters with Sin3a and is essential to maintain it on chromatin. Consistent with this, Fam60a depletion phenocopies the loss of Sin3a, leading to decreased proliferation, an extended G1-phase and the deregulation of genes associated with differentiation. Taken together, our data characterise Fam60a as an essential core subunit of a variant Sin3a complex in ES cells required to promote rapid proliferation and to prevent unscheduled differentiation.

2017-05-19 | PXD005464 | Pride

Fam60a defines a embryonic stem cell specific Sin3a/Hdac complex.

Project description:ChIP coupled with NGS identifies genome-wide binding sites of a ES cells specific Sin3a/Hdac complex. The aim of these experiments is to study the role of Fam60a in the Sin3a/Hdac complex. ChIP-Seq experiments reveal that Fam60a is required to maintain high levels of Sin3a binding on target genes in mESCs. Depletion of Fam60a causes a drop of Sin3a binding to target sites. Underlining the function of Fam60a in mES cells, ChIP-seq analysis of Sin3a and Fam60a in mouse fibroblasts reveal strikingly low global binding level of Sin3a to its target genes while Fam60a is absent at these sites.

2017-04-24 | GSE81081 | GEO

The SIN3A/HDAC Corepressor Complex Functionally Cooperates with NANOG to Promote Pluripotency.

Project description:Although SIN3A is required for the survival of early embryos and embryonic stem cells (ESCs), the role of SIN3A in the maintenance and establishment of pluripotency remains unclear. Here, we find that the SIN3A/HDAC corepressor complex maintains ESC pluripotency and promotes the generation of induced pluripotent stem cells (iPSCs). Members of the SIN3A/HDAC corepressor complex are enriched in an extended NANOG interactome and function in transcriptional coactivation in ESCs. We also identified a critical role for SIN3A and HDAC2 in efficient reprogramming of somatic cells. Mechanistically, NANOG and SIN3A co-occupy transcriptionally active pluripotency genes in ESCs and also co-localize extensively at their genome-wide targets in pre-iPSCs. Additionally, both factors are required to directly induce a synergistic transcriptional program wherein pluripotency genes are activated and reprogramming barrier genes are repressed. Our findings indicate a transcriptional regulatory role for a major HDAC-containing complex in promoting pluripotency.

| S-EPMC5328122 | biostudies-literature

The Sin3a/HDAC co-repressor complex cooperates with Nanog in promoting stem cell pluripotency and somatic cell reprogramming

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-02-21 | GSE91022 | GEO

SIN3A regulates porcine early embryonic development by modulating CCNB1 expression

Project description:SIN3A is the central scaffold protein of the SIN3/HDAC transcriptional repressor complex. We previously found that SIN3A participates in the mouse preimplantation development by finetuning HDAC1 expression. However, it remains unresolved if this functional significance of SIN3A was conserved in other mammals. The objective of this work was thus to characterize the expression profiles and the functional role of SIN3A in preimplantation development using non-rodent animal models. RNA-seq results show a large amount of SIN3A mRNA is present in oocytes and early embryos prior to embryonic genome activation and a low amount thereafter, suggesting a maternal origin of SIN3A in all species examined. Interestingly, immunofluorescence data show that SIN3A protein level peaks at 4-cell stage in pigs compared with morula stage in cattle, suggesting a differential role of SIN3A among species. Indeed, SIN3A depletion in early embryos causes a developmental arrest at 2-cell stage in pigs but does not affect bovine early embryonic development. In contrast with mouse data, SIN3A depletion results in only a slight decrease and even no difference in HDAC1 expression in porcine and bovine early embryos, respectively. In addition, HDAC1 knockdown does not cause 2-cell block, however, leads to a reduced blastocyst rate, suggesting the effect of SIN3A depletion on porcine early embryos is independent of HDAC1. By using un-biased RNA-seq approach, we found that CCNB1 transcript level is dramatically reduced. Moreover, CCNB1 knockdown results in a similar phenotype as SIN3A depletion. Injection of exogenous CCNB1 into SIN3A-depleted embryos could partly rescue embryonic development beyond 2-cell stage. In conclusion, our results indicate SIN3A plays an essential role in porcine early embryonic development, which probably involving the regulation of CCNB1 expression.

2020-09-16 | GSE157650 | GEO

Mus musculus

Project description:The Sin3a/HDAC co-repressor complex cooperates with Nanog in promoting stem cell pluripotency and somatic cell reprogramming [Microarray Expression]

| PRJNA356573 | ENA

Mus musculus

Project description:The Sin3a/HDAC co-repressor complex cooperates with Nanog in promoting stem cell pluripotency and somatic cell reprogramming [ChIP-Seq]

| PRJNA356691 | ENA

Fam60a defines a variant Sin3a-Hdac complex in embryonic stem cells required for self-renewal

Project description:RNA-Sequencing (RNA-seq). The aim of this RNA-seq experiment was to monitor the genome-wide transcriptional changes in mouse embryonic stem cells depleted of either Fam60a or Sin3a.

2017-05-16 | GSE87084 | GEO

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