Genome-wide maps of Sin3A and Sin3B binding in C2C12 myoblasts and differentiated myotubes
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE22554 | GEO | 2011/01/01
SECONDARY ACCESSION(S): PRJNA128453
REPOSITORIES: GEO
Similar Datasets
Project description:Sin3A and Sin3B bind to distinct and overlapping target sites. Sin3 proteins bind to distinct sites in cycling myoblasts whereas there is a converge of Sin3A and Sin3B proteins to sites in differentiated myotubes. We identified a subset of Sin3 target genes involved in muscle differentiation and physiology and showed that conditional ablation of Sin3 proteins in vivo in mouse results in sarcomere defects Examination of Sin3A and Sin3B binding during myogenesis
2011-01-01 | E-GEOD-22554 | biostudies-arrayexpress
Project description:Proteins involved in transcriptional regulation harbor a demonstrated enrichment of mutations in neurodevelopmental disorders. The Sin3 (Swi-independent 3)/histone deacetylase (HDAC) complex plays a central role in histone deacetylation and transcriptional repression. Among the two vertebrate paralogs encoding the Sin3 complex, SIN3A variants cause syndromic intellectual disability, but the clinical consequences of SIN3B haploinsufficiency in humans are uncharacterized. Here, we describe a syndrome hallmarked by intellectual disability, developmental delay, and dysmorphic facial features with variably penetrant autism spectrum disorder, congenital malformations, corpus callosum defects, and impaired growth caused by disruptive SIN3B variants. Using chromosomal microarray or exome sequencing, and through international data sharing efforts, we identified nine individuals with heterozygous SIN3B deletion or single-nucleotide variants. Five individuals harbor heterozygous deletions encompassing SIN3B that reside within a ~230 kb minimal region of overlap on 19p13.11, two individuals have a rare nonsynonymous substitution, and two individuals have a single-nucleotide deletion that results in a frameshift and predicted premature termination codon. To test the relevance of SIN3B impairment to measurable aspects of the human phenotype, we disrupted the orthologous zebrafish locus by genome editing and transient suppression. The mutant and morphant larvae display altered craniofacial patterning, commissural axon defects, and reduced body length supportive of an essential role for Sin3 function in growth and patterning of anterior structures. To investigate further the molecular consequences of SIN3B variants, we quantified genome-wide enhancer and promoter activity states by using H3K27ac ChIP-seq. We show that, similar to SIN3A mutations, SIN3B disruption causes hyperacetylation of a subset of enhancers and promoters in peripheral blood mononuclear cells. Together, these data demonstrate that SIN3B haploinsufficiency leads to a hitherto unknown intellectual disability/autism syndrome, uncover a crucial role of SIN3B in the central nervous system, and define the epigenetic landscape associated with Sin3 complex impairment.
2021-03-31 | GSE171119 | GEO
Project description:mRNA expression analysis of arrested HCT116 cells (wild-type or SIN3B-/-) transfected with either non-targeting control siRNA or one of three SIN3A siRNAs and treated with Idasanulin to activate p53.
2023-10-28 | GSE240734 | GEO
Project description:Transcription products influenced by decreased SIN3A or SIN3B are analyzed and compared.
2020-12-01 | GSE123861 | GEO
Project description:Analysis of gene expression in Idasanutlin-arrested SIN3A and SIN3B depleated cells
| PRJNA1005179 | ENA
Project description:SIN3 associates with RPD3 and other accessory proteins to form the SIN3 histone modifying complex. A single Sin3A gene encodes multiple SIN3 isoforms, of which SIN3 187 and SIN3 220 are predominant. Previous studies from our laboratory and others have indicated that SIN3 isoforms play non-redundant roles during fly development, however, the genes regulated by SIN3 isoforms are not known. We mapped the genome-wide binding sites of SIN3 isoforms in Drosophila. We established stable S2 cell lines that express either HA-tagged SIN3 187 or SIN3 220. The binding profiles revealed that the majority of the binding sites of SIN3 isoforms are overlapping. Our data revealed that SIN3 isoforms localize to euchromatic regions of the genome and enrichment of SIN3 isoforms are generally concentrated around the transcription start sites of genes. In addition, the extent of SIN3 binding confirmed previous findings indicating that SIN3 is a global transcriptional regulator.
2016-01-09 | GSE72171 | GEO
Project description:We report the application of single-molecule-based sequencing technology for REST and its cofactors genome wide binding sites in E14 cells.We then combine these binding sirtes with REST regulating gene profiling, to understand REST binding and regulation in E14 cells. Examination of REST and 5 cofactors(RCOR1, RCOR2,RCOR3,SIN3A,SIN3B) in E14 cells, REST and SIN3A endogenous antibody were used for ChIP experiment. The stable E14 cells expressing low level exogenous RCOR1, RCOR2, RCOR3,and SIN3B with V5 tag were used for ChIP experiment with V5 antibody to obtain individual ChIP DNA.
2011-04-01 | E-GEOD-28233 | biostudies-arrayexpress
Project description:SIN3 associates with RPD3 and other accessory proteins to form the SIN3 histone modifying complex. A single Sin3A gene encodes multiple SIN3 isoforms, of which SIN3 187 and SIN3 220 are predominant. Previous studies from our laboratory and others have indicated that SIN3 isoforms play non-redundant roles during fly development, however, the genes regulated by SIN3 isoforms are not known. We mapped the genome-wide binding sites of SIN3 isoforms in Drosophila. We established stable S2 cell lines that express either HA-tagged SIN3 187 or SIN3 220. The binding profiles revealed that the majority of the binding sites of SIN3 isoforms are overlapping. Our data revealed that SIN3 isoforms localize to euchromatic regions of the genome and enrichment of SIN3 isoforms are generally concentrated around the transcription start sites of genes. In addition, the extent of SIN3 binding confirmed previous findings indicating that SIN3 is a global transcriptional regulator. Genome-wide binding analysis of SIN3 187 and SIN3 220 in Drosophila. Using chromatin prepared from cell lines expressing either of the isoforms, we performed chromatin immunoprecipitation on chromatin prepared from cells that expresses either of the isoforms using an antibody against HA (ChIP). We coupled our ChIP with high resolution deep sequencing (ChIP-seq) to identify genomic targets of SIN3 isoforms.
2016-01-09 | E-GEOD-72171 | biostudies-arrayexpress
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: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