Methylation specifies distinct estrogen-induced binding site repertoires of CBP to chromatin
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE32350 | GEO | 2011/10/07
SECONDARY ACCESSION(S): PRJNA147247
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE32348: Methylation specifies distinct estrogen-induced binding site repertoires of CBP to chromatin (mRNA) GSE32349: Methylation specifies distinct estrogen-induced binding site repertoires of CBP to chromatin (ChIP-Seq) Refer to individual Series
2011-10-06 | E-GEOD-32350 | biostudies-arrayexpress
Project description:Multiple signaling pathways ultimately modulate the epigenetic information embedded in the chromatin of gene promoters by recruiting epigenetic enzymes. We found that, in estrogen-regulated gene programming, the acetyltransferase CREB-binding protein (CBP) is specifically and exclusively methylated by the coactivator-associated arginine methyltransferase (CARM1) in vivo. CARM1-dependent CBP methylation and p160 coactivators were required for estrogen-induced recruitment to chromatin targets. Notably, methylation increased the histone acetyltransferase (HAT) activity of CBP and stimulated its autoacetylation. Comparative genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) studies revealed a variety of patterns by which p160, CBP, and methyl-CBP (meCBP) are recruited (or not) by estrogen to chromatin targets. Moreover, significant target gene-specific variation in the recruitment of (1) the p160 RAC3 protein, (2) the fraction of a given meCBP species within the total CBP, and (3) the relative recruitment of different meCBP species suggests the existence of a target gene-specific “fingerprint” for coregulator recruitment. Crossing ChIP-seq and transcriptomics profiles revealed the existence of meCBP “hubs” within the network of estrogen-regulated genes. Together, our data provide evidence for an unprecedented mechanism by which CARM1-dependent CBP methylation results in gene-selective association of estrogen-recruited meCBP species with different HAT activities and specifies distinct target gene hubs, thus diversifying estrogen receptor programming. Examination of estrogen-induced transcription in H3396 cells
2011-10-06 | E-GEOD-32348 | biostudies-arrayexpress
Project description:Multiple signaling pathways ultimately modulate the epigenetic information embedded in the chromatin of gene promoters by recruiting epigenetic enzymes. We found that, in estrogen-regulated gene programming, the acetyltransferase CREB-binding protein (CBP) is specifically and exclusively methylated by the coactivator-associated arginine methyltransferase (CARM1) in vivo. CARM1-dependent CBP methylation and p160 coactivators were required for estrogen-induced recruitment to chromatin targets. Notably, methylation increased the histone acetyltransferase (HAT) activity of CBP and stimulated its autoacetylation. Comparative genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) studies revealed a variety of patterns by which p160, CBP, and methyl-CBP (meCBP) are recruited (or not) by estrogen to chromatin targets. Moreover, significant target gene-specific variation in the recruitment of (1) the p160 RAC3 protein, (2) the fraction of a given meCBP species within the total CBP, and (3) the relative recruitment of different meCBP species suggests the existence of a target gene-specific “fingerprint” for coregulator recruitment. Crossing ChIP-seq and transcriptomics profiles revealed the existence of meCBP “hubs” within the network of estrogen-regulated genes. Together, our data provide evidence for an unprecedented mechanism by which CARM1-dependent CBP methylation results in gene-selective association of estrogen-recruited meCBP species with different HAT activities and specifies distinct target gene hubs, thus diversifying estrogen receptor programming.
2011-10-07 | GSE32348 | GEO
Project description:Multiple signaling pathways ultimately modulate the epigenetic information embedded in the chromatin of gene promoters by recruiting epigenetic enzymes. We found that, in estrogen-regulated gene programming, the acetyltransferase CREB-binding protein (CBP) is specifically and exclusively methylated by the coactivator-associated arginine methyltransferase (CARM1) in vivo. CARM1-dependent CBP methylation and p160 coactivators were required for estrogen-induced recruitment to chromatin targets. Notably, methylation increased the histone acetyltransferase (HAT) activity of CBP and stimulated its autoacetylation. Comparative genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) studies revealed a variety of patterns by which p160, CBP, and methyl-CBP (meCBP) are recruited (or not) by estrogen to chromatin targets. Moreover, significant target gene-specific variation in the recruitment of (1) the p160 RAC3 protein, (2) the fraction of a given meCBP species within the total CBP, and (3) the relative recruitment of different meCBP species suggests the existence of a target gene-specific âfingerprintâ for coregulator recruitment. Crossing ChIP-seq and transcriptomics profiles revealed the existence of meCBP âhubsâ within the network of estrogen-regulated genes. Together, our data provide evidence for an unprecedented mechanism by which CARM1-dependent CBP methylation results in gene-selective association of estrogen-recruited meCBP species with different HAT activities and specifies distinct target gene hubs, thus diversifying estrogen receptor programming. Examination of estrogen-induced binding site in H3396 cells under Estrogen (E2) or Ethanol (EtOH) treatment: CBP in E2; CBP in EtOH (two technical replicate); CBPR742m in E2 (two technical replicates); CBPR768m in E2; CBPR768m in EtOH; CBPR2151m in E2; CBPR2151m in EtOH; Estrogen receptor alpha (ERa) in E2; ERa in EtOH; Total Histone 3 and 4 acetylated in E2; H3K18ac in E2; H3K18ac in EtOH; Polymerase II (PolII) in E2; PolII in EtOH; RAC3 in E2; Input DNA sample in E2
2011-10-06 | E-GEOD-32349 | biostudies-arrayexpress
Project description:Multiple signaling pathways ultimately modulate the epigenetic information embedded in the chromatin of gene promoters by recruiting epigenetic enzymes. We found that, in estrogen-regulated gene programming, the acetyltransferase CREB-binding protein (CBP) is specifically and exclusively methylated by the coactivator-associated arginine methyltransferase (CARM1) in vivo. CARM1-dependent CBP methylation and p160 coactivators were required for estrogen-induced recruitment to chromatin targets. Notably, methylation increased the histone acetyltransferase (HAT) activity of CBP and stimulated its autoacetylation. Comparative genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) studies revealed a variety of patterns by which p160, CBP, and methyl-CBP (meCBP) are recruited (or not) by estrogen to chromatin targets. Moreover, significant target gene-specific variation in the recruitment of (1) the p160 RAC3 protein, (2) the fraction of a given meCBP species within the total CBP, and (3) the relative recruitment of different meCBP species suggests the existence of a target gene-specific âfingerprintâ for coregulator recruitment. Crossing ChIP-seq and transcriptomics profiles revealed the existence of meCBP âhubsâ within the network of estrogen-regulated genes. Together, our data provide evidence for an unprecedented mechanism by which CARM1-dependent CBP methylation results in gene-selective association of estrogen-recruited meCBP species with different HAT activities and specifies distinct target gene hubs, thus diversifying estrogen receptor programming.
2011-10-07 | GSE32349 | GEO
Project description:Estrogen receptors ERalpha and ERbeta, members of the nuclear receptor superfamily, exert profound effects on the gene expression and biological response programs of their target cells. Herein, we explore the dynamic interplay between these two receptors in their selection of chromatin binding sites when present separately or together in MCF-7 breast cancer cells. Treatment of cells (containing ERalpha only, ERbeta only, or ERalpha and ERbeta) with estradiol or ER subtype-selective ligands was followed by chromatin immunoprecipitation analysis with a custom-designed tiling array for ER binding sites across the genome to examine the effects of ligand-occupied and unoccupied ERalpha and ERbeta on chromatin binding. There was substantial overlap in binding sites for these estradiol-liganded nuclear receptors when present alone, but many fewer sites were shared when both ERs were present. Each ER restricted the binding site occupancy of the other, with ERalpha generally being dominant. Binding sites of both receptors were highly enriched in estrogen response element motifs, but when both ERs were present, ERalpha displaced ERbeta, shifting it into new sites less enriched in estrogen response elements. Binding regions of the two ERs also showed differences in their enrichments for other transcription factor binding motifs. Studies with ER subtype-specific ligands revealed that it was the liganded subtype that principally determined the spectrum of chromatin binding. These findings highlight the dynamic interplay between the two ERs in their selection of chromatin binding sites, with competition, restriction, and site shifting having important implications for the regulation of gene expression by these two nuclear receptors.
| S-EPMC2802902 | biostudies-literature
Project description:Research backgroundDuring the current SARS-CoV2 pandemic, as well as earlier SARS and MERS epidemics, it has been observed that COVID19-positive women on average tend to have milder symptoms and lower fatality rates than men. There is a number of differences between the sexes known to contribute to different immune responses and severity of the disease, one being the effect of estrogen via estrogen receptor signalling. We wondered if estrogen might also affect the SARS-CoV2 more directly, perhaps by binding to the surface glycoprotein (S protein), thus possibly reducing its infectivity.Experimental approachTo assess whether there is a possibility for estrogen binding on the SARS-CoV2 S protein, we used BLAST and HHpred to compare protein sequences of S protein and human estrogen receptor β, while 3D structures of a potential estrogen binding site and an active site of estrogen receptor β were visualized and compared using PyMOL.Results and conclusionsBy comparing the sequence of SARS-CoV2 S protein with the human estrogen receptor β, we identified a potential estrogen binding site on S protein and further determined that it also shares notable similarities with the active site of ER β when observed in 3D structure of their respective proteins. As a control, SARS-CoV2 S protein was compared with the human androgen receptor, and no such similarities were found. The potential estrogen binding site is part of coronavirus S2 superfamily domain, which is involved in host-virus membrane fusion during infection and appears to be conserved throughout the Coronaviridae family.Novelty and scientific contributionThis preliminary communication shows that SARS-CoV2 S protein features a potential estrogen binding site. Hopefully, this will prompt a more comprehensive study on the possibilities of estrogen binding on the S protein and the effect this might confer on the virus infectivity.
| S-EPMC8157085 | biostudies-literature
Project description:MCF-7 breast cancer cells were treated with estradiol and then chromatin immunoprecipitation assays were performed to isolate estrogen receptor and associated genomic DNA binding sites. Keywords: ChIP-on-chip samples
2006-09-05 | GSE5405 | GEO
Project description:MCF-7 breast cancer cells were treated with estradiol and then chromatin immunoprecipitation assays were performed to isolate estrogen receptor and associated genomic DNA binding sites. ChIP DNA fragments were end-labeled with biotinylated nucleotides and then labeled with Cy3-avidin and hybridized to human promoter arrays to detect estrogen receptor binding sites.
2010-07-01 | E-GEOD-5405 | biostudies-arrayexpress
Project description:Pontin is a chromatin remodeling factor that possesses both ATPase and DNA helicase activities. Although Pontin is frequently overexpressed in human cancers of various types and implicated in oncogenic functions, the upstream signaling network leading to the regulation of Pontin that in turn affects transcription of downstream target genes has not been extensively studied. Here, we identify Pontin is methylated by G9a/GLP methyltransferases in hypoxic condition and potentiates HIF-1?-mediated activation by increasing the recruitment of p300 coactivator to a subset of HIF-1? target promoters. Intriguingly, Pontin methylation results in the increased invasive and migratory properties by activating downstream target gene, Ets1. In contrast, inhibition of Pontin methylation results in the suppression of tumorigenic and metastatic properties. Together, our data provide new approaches by targeting Pontin methylation and its downstream targets for the development of therapeutic agents for human cancers.
| S-EPMC3158161 | biostudies-literature