Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Conserved molecular interactions within MYST-ING acetyltransferase complexes that regulate cell proliferation

ABSTRACT: This SuperSeries is composed of the following subset Series: GSE33007: Genome-wide map of HBO1 in cancer derived human cell line GSE33220: Effects of the JADE-HBO1 complex on gene expression Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Eric Paquet

PROVIDER: E-GEOD-33221 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Conserved molecular interactions within the HBO1 acetyltransferase complexes regulate cell proliferation.

Avvakumov Nikita N Lalonde Marie-Eve ME Saksouk Nehmé N Paquet Eric E Glass Karen C KC Landry Anne-Julie AJ Doyon Yannick Y Cayrou Christelle C Robitaille Geneviève A GA Richard Darren E DE Yang Xiang-Jiao XJ Kutateladze Tatiana G TG Côté Jacques J

Molecular and cellular biology 20111205 3

Acetyltransferase complexes of the MYST family with distinct substrate specificities and functions maintain a conserved association with different ING tumor suppressor proteins. ING complexes containing the HBO1 acetylase are a major source of histone H3 and H4 acetylation in vivo and play critical roles in gene regulation and DNA replication. Here, our molecular dissection of HBO1/ING complexes unravels the protein domains required for their assembly and function. Multiple PHD finger domains pr ...[more]

PMID: 22144582

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Project description:Cellular diversity in a multicellular organism like the human is achieved in part by distinct programs of gene expression at the level of transcription, which in turn are mediated by transcription factors (TFs). However, there are few systematic studies of the genomic binding of different types of TFs across a wide range of human cell types, especially in relation to gene expression. Using chromatin Immunoprecipitation followed by thigh-throughput sequencing (ChIP-seq) we identified an average of 45,000, 30,000 and 8,000 binding sites for CTCF, Pol2 and MYC respectively across eleven cell types.CTCF preferred to bind to intergenic regions while Pol2 and MYC tended to bind to core promoter regions. CTCF sites were highly conserved across diverse cell types, whereas MYC showed the greatest cell-type specificity. MYC co-localized with Pol2 at many of their binding sites and putative target genes. Cell-type specific binding sites, in particular for MYC and Pol II, were associated with cell-type specific functions. Patterns of binding in relation to gene features were generally invariant across different cell types. Pol II occupancy was higher over exons than adjacent introns, likely reflecting a link between transcriptional elongation and splicing. TF binding was positively correlated with the expression levels of their putative target genes, but combinatorial binding, in particular of MYC and Pol II was even more strongly associated with higher gene expression. Our ChIP-seq data sheds considerable light on how these transcription factors of different types function individually and in combination with one another to occupy target genomic loci and shape gene expression programs in a cell-type specific manner. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf Keywords: Genome binding/occupancy profiling by high throughput sequencing ChIP-seq were performed on eleven human cell lines: GM12878 (lymphoblastoid), K562 (leukemia), HepG2 (hepatocellular carcinoma), HelaS3 (cervical carcinoma), HUVEC (human umbilical vein endothelial cells), NHEK (keratinocytes), H1-ES (embryonic stem cells), MCF7 (breast adenocarcinoma), FB8470 (Normal child fibroblasts), FB0167P (Progeria fibroblast), and H54 (glioblastoma). For each cell line, two or three replicates were independently grown and split into three, one for each of the three experimental methods. Control ChIP experiments were performed on five of the cell lines with NHEK and H1-ES being excluded due to lack of material. Additional ChIP-Seq data mentioned in the 'overall design' but not included in this Series are contained in the GSE30226 SubSeries.

Project description:The human body contains thousands of unique cell types, each with specialized functions. Cell identity is governed in large part by gene transcription programs, which are determined by regulatory elements encoded in DNA. To identify regulatory elements active in seven cell lines representative of diverse human cell types, we used DNase-seq and FAIRE-seq to map M-CM-"M-BM-^@M-BM-^\open chromatinM-CM-"M-BM-^@M-BM-^]. Over 870,000 DNaseI or FAIRE sites, which correspond largely to nucleosome depleted regions (NDRs), were identified across the seven cell lines, covering nearly 9% of the genome. The combination of DNaseI and FAIRE is more effective than either assay alone in identifying likely regulatory elements, as judged by coincidence with transcription factor binding locations determined in the same cells. Open chromatin common to all seven cell types tended to be at or near transcription start sites and encompassed more CTCF binding sites, while open chromatin sites found in only one cell type were typically located away from transcription start sites, and contained DNA motifs recognized by regulators of cell-type identity. As one example of its ability to identify functional DNA, we show that open chromatin regions bound by CTCF are potent insulators. We identified clusters of open regulatory elements (COREs) that were physically near each other and whose appearance was coordinated among one or more cell types. Gene expression and RNA Pol II binding data support the hypothesis that COREs control gene activity required for the maintenance of cell-type identity. This publicly available atlas of regulatory elements may prove valuable in identifying non-coding DNA sequence variants that are causally linked to human disease. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf DNase-seq, FAIRE-seq, and ChIP-seq were performed on seven human cell lines: GM12878 (lymphoblastoid), K562 (leukemia), HepG2 (hepatocellular carcinoma), HelaS3 (cervical carcinoma), HUVEC (human umbilical vein endothelial cells), NHEK (keratinocytes), and H1-ES (embryonic stem cells). For each cell line, two or three replicates were independently grown and split into three, one for each of the three experimental methods. Control ChIP experiments were performed on five of the cell lines with NHEK and H1-ES being excluded due to lack of material.

Dataset Information

Conserved molecular interactions within MYST-ING acetyltransferase complexes that regulate cell proliferation

Publications

Conserved molecular interactions within the HBO1 acetyltransferase complexes regulate cell proliferation.

Similar Datasets

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