Fam60a defines a variant Sin3a-Hdac complex in embryonic stem cells required for self-renewal
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE87084 | GEO | 2017/05/16
SECONDARY ACCESSION(S): PRJNA343472
REPOSITORIES: GEO
Similar Datasets
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
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
Project description: Not available
| S-EPMC5538769 | biostudies-literature
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
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 | GSE90986 | GEO
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
Project description:Tyrosine phosphorylation is a hallmark for activation of Signal Transducer and Activator of Transcription (STAT) proteins, but their transcriptional activity also depends on other secondary modifications. Type I interferons (IFNs) can activate both the ISGF3 (STAT1:STAT2:IRF9) complex and STAT3, but with cell-specific, selective triggering of only the ISGF3 transcriptional program. Following a genome-wide RNAi screen, we identified the Sin3a complex as an important mediator of this STAT3 transcriptional repression. Sin3a directly interacts with the DNA-binding domain of STAT3 and alters its acetylation status. SIN3A silencing enhances recruitment of STAT3 and enhanceosome components to the SOCS3 promoter, resulting in histone hyperacetylation and enhanced transcription. Conversely, Sin3a is required for ISGF3-dependent gene transcription and for an efficient IFN-mediated antiviral protection against Influenza A and hepatitis C viruses. The Sin3a complex therefore acts as a context-dependent STAT1/3 transcriptional switch. MCF7 cells were transfected with 50nM Renilla luciferase (control) or SIN3A-specific siRNA. 72h later, cells were cultured for 4h in absence of FCS and left non-stimulated or stimulated with LIF (10ng/ml, 1h). Total RNA was extracted. For each of the 4 conditions, 3 biological replicates were included. Nevertheless, one sample (SIN3A_siRNA_LIF1h_rep3) was discarded. In total 11 samples were analyzed.
2012-08-01 | E-GEOD-35696 | biostudies-arrayexpress
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2020-04-11 | GSE146474 | GEO
Project description:Comparison of global transcription profiles in mouse E12.5 embryonic lung from Shh-Cre;Sin3a flox/+ control with Shh-Cre;Sin3a flox/flox revealed a large change genes due to loss of Sin3a in early lung development.
2017-06-22 | GSE94306 | GEO