Estrogen Regulates the JNK1 Genomic Localization Program in Breast Cancer Cells to Control Gene Expression and Cell Growth
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: W. Lee Kraus
PROVIDER: E-GEOD-13200 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:We are studying the mechanisms by which the estrogen receptor, ERalpha, is recruited to and regulates genes with a non-direct DNA binding. We performed ChIP-chip for ERalpha in E2 treated HeLa-ER cells, and looked at 19000 RefSeq genes to determine binding patterns of the receptor at promoters. The experiment was performed in duplicate. ChIP-chip biological replicates for Eralpha in E2 treated HeLa-ER cells are included.
2011-02-22 | E-GEOD-22099 | biostudies-arrayexpress
Project description:Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a transcriptional coactivator that has previously been shown to collaborate with nuclear receptors. Evidence from other groups suggest that PELP1 may stimulate transcription by displacing the linker histone H1 and/or by recruiting the lysine demethylase KDM1 to demethylate H3K9me2. Also known as modulator of the non-genomic activity of estrogen receptor (MNAR), PELP1 has also been implicated promoting estrogen receptor signaling from the plasma membrane. We recently identified PELP1 a factor that interacts with the macro domain of the histone variant macroH2A1. To determine if PELP1 interacts with macroH2A1 in cells, we performed PELP1 ChIP-chip from MCF-7 cells. The pattern of PELP1 bind across the genome strongly correlates with that previously determined for macroH2A1. This data combined with additional experiments allow us to conclude that macroH2A1 regulates target gene expression in part by recruiting the transcriptional coregulator PELP1. Two PELP1 ChIP-chip biological replicates from MCF-7 human breast cancer cells are included.
2014-04-24 | E-GEOD-22254 | biostudies-arrayexpress
Project description:Estrogen receptor M-NM-1 (ER), a member of the nuclear hormone receptor superfamily, regulates transcriptional activity by ligand-dependent recruitment of cofactors which, in turn, locally alter chromatin structure. It is generally believed that co-factor activity at target promoters leads to a more open, transcriptionally permissive chromatin structure, however, these mechanisms remain to be fully established. Peptidylarginine deiminases (PADIs) catalyze the conversion of positively charged arginine and methylarginine residues to neutrally charged citrulline and this activity has been linked to the gene regulation. Here, we found that PADI2 citrullinate H3 Arginine 26 (H3R26) in vitro and, using a specific H3R26 citrulline (H3Cit26) antibody, we demonstrate that H3Cit26 occurs in vivo following 17M-NM-2-estradiol (E2) stimulation and this unique and pronounced global activation of H3Cit26 is ER-dependent. Using a mammalian-based promoter chromosomal array system, we observed that citrullination at H3R26 is robust and co-localizes with ER at decondensed chromatin loci. Additionally, this histone modification is specifically enriched at ER bound regions of target promoters, forming a permissive chromatin environment for gene transactivation. Interestingly, we have shown in a reciprocal way, that either depletion of PADI2 or inhibition of ER not only dramatically abolished E2-induced activation of H3Cit26 on gene promoters but also affect ER recruitment. Collectively, our results demonstrate that citrullination of H3R26 by PADI2 following estrogen stimulation plays a role in ER target gene activation, likely via decondensation of the local chromatin architecture. Two H3Cit26 ChIP-chip biological replicates under vehicle treatment and two H3Cit26 ChIP-chip biological replicates under E2 stimulation from MCF-7 human breast cancer cells are included.
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Project description:MacroH2A1 ChIP-chip was performed on custom Nimblegen genomic tiling arrays, to understand the genomic binding patterns of this histone variant and its relationship to gene expression Keywords: ChIP-chip Two macroH2A biological replicates are included. An H3 ChIP-chip sample is included as a control
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Project description:We are examining the mechanisms by which the nuclear enzyme PARP-1 regulates gene expression. We performed ChIP-chip for PARP-1, histone H3 and H3K4me3 (lysine 4 trimethylation on histone H3) in MCF7 breast carcinoma cells, and looked at 23550 RefSeq genes to determine binding patterns of these factors at promoters. Each experiment was performed in duplicate. ChIP-chip biological replicates for PARP-1, H3 and H3K4me3 (2 replicates each) from MCF7 human breast carcinoma cells are included.
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Project description:MacroH2A1 is a histone variant that is enriched on the inactive X chromosome (Xi) in mammals and is postulated to play an important, but unknown, role in the repression of gene expression. Here we show that although macroH2A1 marks repressed autosomal chromatin, it positively regulates transcription when located in the transcribed regions of many target genes. We used chromatin immunoprecipitation coupled with tiling microarrays (ChIP-chip) to determine the genomic localization of macroH2A1 in IMR90 human primary lung fibroblasts and MCF-7 breast cancer cells. The patterns of macroH2A1 deposition are largely similar across the autosomes of both cell lines. Our studies revealed a genomic localization pattern unique among histone variants, namely the occupation by macroH2A1 of large chromatin domains (>500 kb in some cases) that contain repressive chromatin marks (e.g., histone H3 lysine 27 trimethylation). The boundaries of macroH2A1-containing domains tend to occur in promoter proximal regions. Not all promoters, however, serve as macroH2A1 boundaries; many macroH2A1-containing chromatin domains invade the transcribed regions of genes whose products play key roles in development and cell-cell signaling. Surprisingly, the expression of many of these genes is positively regulated by macroH2A1. MacroH2A1 also plays a role in augmenting signal-regulated transcription, specifically for genes responsive to serum starvation. Collectively, our results document an unexpected role for macroH2A1 in the escape from heterochromatin-associated silencing and the enhancement of autosomal gene transcription. Two macroH2A1 ChIP-chip biological replicates from IMR90 human embryonic lung fibroblasts are included.
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