Expression data from Panc1 pancreatic epithelial cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE56778 | GEO | 2014/08/01
SECONDARY ACCESSION(S): PRJNA244565
REPOSITORIES: GEO
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2016-01-09 | E-GEOD-72171 | biostudies-arrayexpress
Project description:Histone deacetylase 1 and 2 (HDAC1/2) are highly related enzymes that that regulate histone acetylation levels in all cells, as catalytic and structural components of six unique multi-protein complexes: SIN3, NuRD, CoREST, MIDAC, MIER1 and RERE. Co-immunoprecipitation of HDAC1-Flag followed by mass-spectrometry revealed that 92% of the HDAC1 in mouse embryonic stem cells resides in 3 complexes, NuRD (49%), CoREST (28%) and SIN3 (15%). To delineate the function of these different biochemical entities we compared binary structures of the MTA1:HDAC1 and MIDAC:HDAC1 to identify conserved residues on the surface of HDAC1 that would potentially perturb one or more complexes. A single mutation, Y48E, disrupts binding to all complexes with the exception of SIN3. Remarkably, rescue experiments performed with HDAC1-Y48E in HDAC1/2 double-knockout cells, showed that retention of SIN3 binding alone is sufficient for cell viability. Gene expression and histone acetylation patterns were perturbed in both Y48E and a second mutant cell line, HDAC1-E63R, indicating that cells require a full repertoire of the HDAC1/2 complexes to regulate their transcriptome appropriately. Comparative analysis of SIN3/HDAC1 and MTA1/HDAC1 structures confirmed the differential modes of HDAC1 recruitment, with the surface including Y48 bound only by ELM2/SANT domain containing complexes. We provide novel molecular insights into the abundance, co-factors and assemblies of this crucial family of chromatin modifying machines.
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Project description:The multi-subunit Sin3 co-repressor complex regulates gene transcription through deacetylation of nucleosomes. However, the full range of Sin3 activities and targets is not well understood. Here, we have investigated genome-wide binding of mouse Sin3 and RBP2 as well as histone modifications and nucleosome positioning as a function of myogenic differentiation. Remarkably, we find that Sin3 complexes spread immediately downstream of the transcription start site on repressed and transcribed genes during differentiation. We show that RBP2 is part of a Sin3 complex, and on a subset of E2F4 target genes, the coordinated activity of Sin3 and RBP2 leads to deacetylation, demethylation, and repositioning of nucleosomes. Our work provides evidence for coordinated binding of Sin3, chromatin modifications, and chromatin remodeling within discrete regulatory regions, suggesting a model in which spreading of Sin3 binding is ultimately linked to permanent gene silencing on a subset of E2F4 target genes.
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Project description:The Sin3 histone deacetylase (HDAC) complex is a 1.2 MDa chromatin modifying complex that can repress transcription by binding to gene promoters and deacetylating histones. The Sin3/HDAC complex can affect cell cycle progression through multiple mechanisms and is among the targets of anticancer drugs, called HDAC inhibitors. We describe the identification of a new subunit of the Sin3 complex named family with sequence similarity 60 member A (FAM60A). We show that FAM60A/Sin3 complexes normally suppress the epithelial-to-mesenchymal transition (EMT) and cell migration. This occurs through transcriptional repression of genes that encode components of the TGF-beta signaling pathway. This work reveals that FAM60A and the Sin3 complex are upstream repressors of TGF-beta signaling, EMT and cell migration and extends the known biological roles of the Sin3 complex. This experiment investigates the role of FAM60A in gene expression by comparing A549 lung cancer cells treated with or without siRNA against FAM60A. The Sin3 histone deacetylase (HDAC) complex is a 1.2 MDa chromatin modifying complex that can repress transcription by binding to gene promoters and deacetylating histones. SDS3 is a core component of the Sin3 complex. The Sin3/HDAC complex can affect cell cycle progression through multiple mechanisms and is among the targets of anticancer drugs, called HDAC inhibitors. We describe the identification of a new subunit of the Sin3 complex named family with sequence similarity 60 member A (FAM60A). We show that FAM60A/Sin3 complexes normally suppress the epithelial-to-mesenchymal transition (EMT) and cell migration. This occurs through transcriptional repression of genes that encode components of the TGF-beta signaling pathway. This work reveals that FAM60A and the Sin3 complex are upstream repressors of TGF-beta signaling, EMT and cell migration and extends the known biological roles of the Sin3 complex. As a base line to better understand the relationship between FAM60A and the Sin3 complex, this experiment investigates the gene expression changes which occur in A549 lung cancer cells when the Sin3 complex is perturbed by knockdown of a core component via siRNA against SDS3. FAM60A siRNA knockdowns were compared to a non-targeting control in triplicate, for a total of 6 samples. SDS3 siRNA knockdowns were compared to a non-targeting control in triplicate, for a total of 6 samples.
2012-09-15 | E-GEOD-39733 | biostudies-arrayexpress
Project description:The Sin3 histone deacetylase (HDAC) complex is a 1.2 MDa chromatin modifying complex that can repress transcription by binding to gene promoters and deacetylating histones. The Sin3/HDAC complex can affect cell cycle progression through multiple mechanisms and is among the targets of anticancer drugs, called HDAC inhibitors. We describe the identification of a new subunit of the Sin3 complex named family with sequence similarity 60 member A (FAM60A). We show that FAM60A/Sin3 complexes normally suppress the epithelial-to-mesenchymal transition (EMT) and cell migration. This occurs through transcriptional repression of genes that encode components of the TGF-beta signaling pathway. This work reveals that FAM60A and the Sin3 complex are upstream repressors of TGF-beta signaling, EMT and cell migration and extends the known biological roles of the Sin3 complex. This experiment investigates the role of FAM60A in gene expression by comparing A549 lung cancer cells treated with or without siRNA against FAM60A. The Sin3 histone deacetylase (HDAC) complex is a 1.2 MDa chromatin modifying complex that can repress transcription by binding to gene promoters and deacetylating histones. SDS3 is a core component of the Sin3 complex. The Sin3/HDAC complex can affect cell cycle progression through multiple mechanisms and is among the targets of anticancer drugs, called HDAC inhibitors. We describe the identification of a new subunit of the Sin3 complex named family with sequence similarity 60 member A (FAM60A). We show that FAM60A/Sin3 complexes normally suppress the epithelial-to-mesenchymal transition (EMT) and cell migration. This occurs through transcriptional repression of genes that encode components of the TGF-beta signaling pathway. This work reveals that FAM60A and the Sin3 complex are upstream repressors of TGF-beta signaling, EMT and cell migration and extends the known biological roles of the Sin3 complex. As a base line to better understand the relationship between FAM60A and the Sin3 complex, this experiment investigates the gene expression changes which occur in A549 lung cancer cells when the Sin3 complex is perturbed by knockdown of a core component via siRNA against SDS3.
2012-09-15 | GSE39733 | GEO
Project description:Here we have characterized the transcriptional processes underlying the formation of human brown in white (i.e. brite) adipocytes using a genome-wide approach. We show that the browning process is associated with reprogramming of peroxisome proliferator-activated receptor γ (PPARγ) binding to form brite adipocyte-selective PPARγ super-enhancers that appear to play a key role in activation of brite adipocyte-selective genes. We identify the KLF11 gene based on its association with a PPARγ super-enhancer and show that KLF11 is a novel browning factor directly induced by rosiglitazone and required for the activation of brite adipocyte-selective gene program by rosiglitazone. Genome-wide profiling of Dnase I hypersenstive (DHS) sites, epigenomic marks, transcription factor and co-factor binding, and gene expression in hMADS white and brite adipocytes
2014-12-12 | E-GEOD-59703 | 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.
2016-01-09 | GSE72171 | GEO
Project description:SIN3 is a master transcriptional scaffold protein. SIN3 interacts with RPD3 and other accessory proteins to form a histone modifying complex. A single Sin3A gene encodes multiple isoforms of SIN3, of which SIN3 187 and SIN3 220 are the predominant isoforms. Previous studies demonstrated that SIN3 isoforms play non-redundant roles during fly development. In the current study, we sought to investigate the genes regulated by SIN3 187. S2 cells and cells carrying a stable transgene of SIN3 187HA (SIN3 187HA cells) were treated with 0.07 µM CuSO4. CuSO4 treatment led to ectopic expression of SIN3 187HA. S2 cells were used as a control. Following induction, total mRNA was extracted. mRNA profiling of these samples were performed by deep sequencing using Illumina Hiseq2500. Three biological replicates were performed.
2016-01-09 | E-GEOD-72172 | biostudies-arrayexpress