CBP/P300 Function in Repression as well as Activation Regulated by Adenovirus Small E1A
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Arnold Berk
PROVIDER: E-GEOD-59693 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Oncogenic transformation by adenovirus small e1a depends on simultaneous interactions with P300/CBP and RB proteins. To understand why, experiments with structure-based e1a mutants were analyzed with RNA- and ChIP-seq. The results indicate that e1a displaces RBs from E2F activation domains and, by promoting P300 acetylation of RB1 K873/K874, locks them into a repressing conformation that interacts with repressive chromatin modifying enzymes. e1a then delivers these repressing p300-e1a-RB1 complexes to cell genes that have unusually high P300 association with the gene body, enriched in genes of the TGFb-, TNF-, and IL1-signaling pathways. The P300-e1a-RB complex condenses chromatin, dependent on HDAC activity, P300 lysine acetylase activity, the P300 bromodomain, and acetylation of RB K873/K874 and e1a K239, contributing to repression of host genes that would otherwise inhibit cell cycling. The data suggest why e1a must bind P300/CBP as well as RBs for oncogenic transformation and why a trimeric P300-e1a-RB1 complex is required. Examination of transcriptome by mRNA sequencing before and after infection by adenoviral e1a expressing vectors in growth arrested IMR90
2014-08-15 | E-GEOD-59688 | biostudies-arrayexpress
Project description:Oncogenic transformation by adenovirus small e1a depends on simultaneous interactions with P300/CBP and RB proteins. To understand why, experiments with structure-based e1a mutants were analyzed with RNA- and ChIP-seq. The results indicate that e1a displaces RBs from E2F activation domains and, by promoting P300 acetylation of RB1 K873/K874, locks them into a repressing conformation that interacts with repressive chromatin modifying enzymes. e1a then delivers these repressing p300-e1a-RB1 complexes to cell genes that have unusually high P300 association with the gene body, enriched in genes of the TGFb-, TNF-, and IL1-signaling pathways. The P300-e1a-RB complex condenses chromatin, dependent on HDAC activity, P300 lysine acetylase activity, the P300 bromodomain, and acetylation of RB K873/K874 and e1a K239, contributing to repression of host genes that would otherwise inhibit cell cycling. The data suggest why e1a must bind P300/CBP as well as RBs for oncogenic transformation and why a trimeric P300-e1a-RB1 complex is required. Examination of RB1 rearrangements by adenoviral e1a as well as mutant e1as in IMR90
2014-08-15 | E-GEOD-59690 | biostudies-arrayexpress
Project description:Oncogenic transformation by adenovirus small e1a depends on simultaneous interactions with P300/CBP and RB proteins. To understand why, experiments with structure-based e1a mutants were analyzed with RNA- and ChIP-seq. The results indicate that e1a displaces RBs from E2F activation domains and, by promoting P300 acetylation of RB1 K873/K874, locks them into a repressing conformation that interacts with repressive chromatin modifying enzymes. e1a then delivers these repressing p300-e1a-RB1 complexes to cell genes that have unusually high P300 association with the gene body, enriched in genes of the TGFb-, TNF-, and IL1-signaling pathways. The P300-e1a-RB complex condenses chromatin, dependent on HDAC activity, P300 lysine acetylase activity, the P300 bromodomain, and acetylation of RB K873/K874 and e1a K239, contributing to repression of host genes that would otherwise inhibit cell cycling. The data suggest why e1a must bind P300/CBP as well as RBs for oncogenic transformation and why a trimeric P300-e1a-RB1 complex is required. Examination of RB1 rearrangements by adenoviral e1a in IMR90
2014-08-15 | E-GEOD-59689 | biostudies-arrayexpress
Project description:Oncogenic transformation by adenovirus small e1a depends on simultaneous interactions with P300/CBP and RB proteins. To understand why, experiments with structure-based e1a mutants were analyzed with RNA- and ChIP-seq. The results indicate that e1a displaces RBs from E2F activation domains and, by promoting P300 acetylation of RB1 K873/K874, locks them into a repressing conformation that interacts with repressive chromatin modifying enzymes. e1a then delivers these repressing p300-e1a-RB1 complexes to cell genes that have unusually high P300 association with the gene body, enriched in genes of the TGFb-, TNF-, and IL1-signaling pathways. The P300-e1a-RB complex condenses chromatin, dependent on HDAC activity, P300 lysine acetylase activity, the P300 bromodomain, and acetylation of RB K873/K874 and e1a K239, contributing to repression of host genes that would otherwise inhibit cell cycling. The data suggest why e1a must bind P300/CBP as well as RBs for oncogenic transformation and why a trimeric P300-e1a-RB1 complex is required. Chromatin IP background Input DNA for ChIP-seq normalization
2014-08-15 | E-GEOD-59692 | biostudies-arrayexpress
Project description:Oncogenic transformation by adenovirus small e1a depends on simultaneous interactions with P300/CBP and RB proteins. To understand why, experiments with structure-based e1a mutants were analyzed with RNA- and ChIP-seq. The results indicate that e1a displaces RBs from E2F activation domains and, by promoting P300 acetylation of RB1 K873/K874, locks them into a repressing conformation that interacts with repressive chromatin modifying enzymes. e1a then delivers these repressing p300-e1a-RB1 complexes to cell genes that have unusually high P300 association with the gene body, enriched in genes of the TGFb-, TNF-, and IL1-signaling pathways. The P300-e1a-RB complex condenses chromatin, dependent on HDAC activity, P300 lysine acetylase activity, the P300 bromodomain, and acetylation of RB K873/K874 and e1a K239, contributing to repression of host genes that would otherwise inhibit cell cycling. The data suggest why e1a must bind P300/CBP as well as RBs for oncogenic transformation and why a trimeric P300-e1a-RB1 complex is required. Examination of POL II rearrangements by adenoviral e1a in IMR90
2014-08-15 | E-GEOD-59691 | biostudies-arrayexpress
Project description:Oncogenic transformation by adenovirus small e1a depends on simultaneous interactions with P300/CBP and RB proteins. To understand why, experiments with structure-based e1a mutants were analyzed with RNA- and ChIP-seq. The results indicate that e1a displaces RBs from E2F activation domains and, by promoting P300 acetylation of RB1 K873/K874, locks them into a repressing conformation that interacts with repressive chromatin modifying enzymes. e1a then delivers these repressing p300-e1a-RB1 complexes to cell genes that have unusually high P300 association with the gene body, enriched in genes of the TGFb-, TNF-, and IL1-signaling pathways. The P300-e1a-RB complex condenses chromatin, dependent on HDAC activity, P300 lysine acetylase activity, the P300 bromodomain, and acetylation of RB K873/K874 and e1a K239, contributing to repression of host genes that would otherwise inhibit cell cycling. The data suggest why e1a must bind P300/CBP as well as RBs for oncogenic transformation and why a trimeric P300-e1a-RB1 complex is required. Examination of H3K27ac IMR90 before and after infection with dl1500
2014-08-15 | E-GEOD-59680 | biostudies-arrayexpress
Project description:Oncogenic transformation by adenovirus small e1a depends on simultaneous interactions with P300/CBP and RB proteins. To understand why, experiments with structure-based e1a mutants were analyzed with RNA- and ChIP-seq. The results indicate that e1a displaces RBs from E2F activation domains and, by promoting P300 acetylation of RB1 K873/K874, locks them into a repressing conformation that interacts with repressive chromatin modifying enzymes. e1a then delivers these repressing p300-e1a-RB1 complexes to cell genes that have unusually high P300 association with the gene body, enriched in genes of the TGFb-, TNF-, and IL1-signaling pathways. The P300-e1a-RB complex condenses chromatin, dependent on HDAC activity, P300 lysine acetylase activity, the P300 bromodomain, and acetylation of RB K873/K874 and e1a K239, contributing to repression of host genes that would otherwise inhibit cell cycling. The data suggest why e1a must bind P300/CBP as well as RBs for oncogenic transformation and why a trimeric P300-e1a-RB1 complex is required. Examination of P300 IMR90 before and after infection with dl1500
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Project description:Adenovirus e1a induces quiescent human cells to divide. We found that e1a causes global relocalization of the RB-proteins (RB, p130, p107) and p300/CBP histone acetyltransferases on promoters that restricts H3K18ac to a limited set of genes to stimulate cell cycling and inhibit antiviral responses and cellular differentiation. Soon after expression, e1a binds transiently to cell cycle/growth genes, causing enrichment of p300/CBP, PCAF, H3K18ac, depletion of RB-proteins, and transcriptional activation. e1a also associates transiently with antiviral genes, causing enrichment for RB, p130, H4K16ac, increased nucleosome density, and repression. At later times, e1a and p107 bind mainly to development/differentiation genes, repressing transcription. The temporal order of e1a binding required its interactions with p300/CBP and RB-proteins. Our data uncover a defined transcriptional and epigenetic reprogramming leading to cellular transformation. Expression profiles and ChIP on chip genomewide experiments with dl1500 virus (expressing WT small e1a).
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Project description:Adenovirus e1a induces quiescent human cells to divide. We found that e1a causes global relocalization of the RB-proteins (RB, p130, p107) and p300/CBP histone acetyltransferases on promoters that restricts H3K18ac to a limited set of genes to stimulate cell cycling and inhibit antiviral responses and cellular differentiation. Soon after expression, e1a binds transiently to cell cycle/growth genes, causing enrichment of p300/CBP, PCAF, H3K18ac, depletion of RB-proteins, and transcriptional activation. e1a also associates transiently with antiviral genes, causing enrichment for RB, p130, H4K16ac, increased nucleosome density, and repression. At later times, e1a and p107 bind mainly to development/differentiation genes, repressing transcription. The temporal order of e1a binding required its interactions with p300/CBP and RB-proteins. Our data uncover a defined transcriptional and epigenetic reprogramming leading to cellular transformation. This SuperSeries is composed of the following subset Series: GSE12045: Expression profiles and ChIP on chip genomewide experiments with dl1500 virus (expressing WT small e1a). GSE12046: Expression profiles and ChIP on chip genomewide experiments with R2G mutant virus GSE12047: Expression profiles and ChIP on chip genomewide experiments with deltaCR2 mutant virus Refer to individual Series
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