Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-54846
PROVIDER: PRJNA237809 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1166800.fastq.gz | Fastqsanger.gz | |||
| SRR1166801.fastq.gz | Fastqsanger.gz | |||
| SRR1166802.fastq.gz | Fastqsanger.gz | |||
| SRR1166803.fastq.gz | Fastqsanger.gz | |||
| SRR1166798.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
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Project description:RNA-seq from control and macroH2A1-depleted IMR90 primary human lung fibroblasts
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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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Project description:The histone variant macroH2A1 and the poly(ADP-ribose) polymerase PARP-1 both regulate gene transcription by modulating chromatin structure and function. Of the two macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, the former is often suppressed in cancer and has the unique ability to interact with poly(ADP-ribose). Using ChIP-seq in primary lung fibroblasts, we demonstrate that macroH2A1 is incorporated into either of two spatially and functionally distinct types of chromatin; the first is marked by H3 K27 trimethylation, while the second contains a set of nine histone acetylations. MacroH2A1-regulated genes are involved in cancer progression are specifically found in macroH2A1-containing acetylated chromatin. Through the recruitment of PARP-1, macroH2A1.1 promotes the acetylation of H2B K12 and K120 which plays a key role in the regulation of macroH2A1 target genes in primary cells. The macroH2A1/PARP-1 pathway regulating H2B K12 and K120 acetylation is disrupted in cancer cells, in part, explaining macroH2A1’s role in cancer suppression. Three biological replicates of RNA-seq from cells expressing shRNA directed against macroH2A1 or luciferase as a control
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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.
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Project description:The histone variant macroH2A1 and the poly(ADP-ribose) polymerase PARP-1 both regulate gene transcription by modulating chromatin structure and function. Of the two macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, the former is often suppressed in cancer and has the unique ability to interact with poly(ADP-ribose). Using ChIP-seq in primary lung fibroblasts, we demonstrate that macroH2A1 is incorporated into either of two spatially and functionally distinct types of chromatin; the first is marked by H3 K27 trimethylation, while the second contains a set of nine histone acetylations. MacroH2A1-regulated genes are involved in cancer progression are specifically found in macroH2A1-containing acetylated chromatin. Through the recruitment of PARP-1, macroH2A1.1 promotes the acetylation of H2B K12 and K120 which plays a key role in the regulation of macroH2A1 target genes in primary cells. The macroH2A1/PARP-1 pathway regulating H2B K12 and K120 acetylation is disrupted in cancer cells, in part, explaining macroH2A1M-bM-^@M-^Ys role in cancer suppression. Two biological replicates of the macroH2A1 ChIP and two corresponding input samples were sequenced
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Project description:The histone variant macroH2A1 and the poly(ADP-ribose) polymerase PARP-1 both regulate gene transcription by modulating chromatin structure and function. Of the two macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, the former is often suppressed in cancer and has the unique ability to interact with poly(ADP-ribose). Using ChIP-seq in primary lung fibroblasts, we demonstrate that macroH2A1 is incorporated into either of two spatially and functionally distinct types of chromatin; the first is marked by H3 K27 trimethylation, while the second contains a set of nine histone acetylations. MacroH2A1-regulated genes are involved in cancer progression are specifically found in macroH2A1-containing acetylated chromatin. Through the recruitment of PARP-1, macroH2A1.1 promotes the acetylation of H2B K12 and K120 which plays a key role in the regulation of macroH2A1 target genes in primary cells. The macroH2A1/PARP-1 pathway regulating H2B K12 and K120 acetylation is disrupted in cancer cells, in part, explaining macroH2A1’s role in cancer suppression.
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