Cell-type specific and combinatorial usage of diverse transcription factors revealed by genome-wide binding studies in multiple human cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE32883 | GEO | 2011/10/18
REPOSITORIES: GEO
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Project description:This SuperSeries is composed of the following subset Series: GSE19622: Individual-specific and allele-specific chromatin signatures in diverse human populations GSE25416: High-resolution genome-wide in vivo footprinting of diverse transcription factors in human cells (ChIP-seq) GSE30226: Open chromatin defined by DNaseI and FAIRE identifies regulatory elements that shape cell-type identity [ChIP_seq]. GSE32692: Cell-type specific and combinatorial usage of diverse transcription factors revealed by genome-wide binding studies in multiple human cells [new ChIP-Seq samples] For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf Refer to individual Series
2011-10-17 | E-GEOD-32883 | biostudies-arrayexpress
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.
2011-10-18 | E-GEOD-32692 | biostudies-arrayexpress
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
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Project description:Cell-type diversity is governed in part by differential gene expression programs mediated by transcription factor (TF) binding. 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. In the ENCODE Project, we have identified the genomic binding locations across 11 different human cell types of CTCF, RNA Pol II (RNAPII), and MYC, three TFs with diverse roles. Our data and analysis revealed how these factors bind in relation to genomic features and shape gene expression and cell-type specificity. CTCF bound predominantly in intergenic regions while RNAPII and MYC preferentially bound to core promoter regions. CTCF sites were relatively invariant across diverse cell types, while MYC showed the greatest cell-type specificity. MYC and RNAPII co-localized at many of their binding sites and putative target genes. Cell-type specific binding sites, in particular for MYC and RNAPII, were associated with cell-type specific functions. Patterns of binding in relation to gene features were generally conserved across different cell types. RNAPII 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 RNAPII, was even more strongly associated with higher gene expression. These data illuminate how combinatorial binding of transcription factors in diverse cell types is associated with gene expression and cell-type specific biology.
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Project description:Using DNaseI hypersensitivity (HS) assays (Dnase-seq), high resolution DNaseI digestion profiles were generated genome-wide in diverse human cell types. We showed that within general regions of DNaseI HS that are known to identify locations of gene regulatory elements, DNaseI digestion patterns allowed us to identify locations of individual transcription factor binding sites that protected against the bound DNA against digestion. To measure the accuracy of these footprints, we also generated ChIP-seq data for the CTCF DNA binding factor in the same cell growths. We found that DNaseI footprints containing the CTCF canonical binding motif show significant ChIP-seq signal while CTCF binding motifs not in footprints show almost no signal providing one measure of valdation of the DNaseI footprints. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf Six cell lines representing cervica carcinoma, chronic myeloid leukemia, human embryonic stem cells, lymphoblastoid cells, human epidermal keratinocytes and umbilical vein endothelial cells were analyzed using Dnase-seq.
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