Proteo-Genomic Characterization and Mapping of Nucleosomes Decoded by Brd and HP1 Proteins
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE39581 | GEO | 2012/07/31
SECONDARY ACCESSION(S): PRJNA171161
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE39579: Proteo-Genomic Characterization and Mapping of Nucleosomes Decoded by Brd and HP1 Proteins (Chip-Seq data) GSE39580: Proteo-Genomic Characterization and Mapping of Nucleosomes Decoded by Brd and HP1 Proteins (expression data) Refer to individual Series
2012-07-30 | E-GEOD-39581 | biostudies-arrayexpress
Project description:BACKGROUND:Histone post-translational modifications (PTMs) constitute a branch of epigenetic mechanisms that can control the expression of eukaryotic genes in a heritable manner. Recent studies have identified several PTM-binding proteins containing diverse specialized domains whose recognition of specific PTM sites leads to gene activation or repression. Here, we present a high-throughput proteogenomic platform designed to characterize the nucleosomal make-up of chromatin enriched with a set of histone PTM binding proteins known as histone PTM readers. We support our findings with gene expression data correlating to PTM distribution. RESULTS:We isolated human mononucleosomes bound by the bromodomain-containing proteins Brd2, Brd3 and Brd4, and by the chromodomain-containing heterochromatin proteins HP1? and HP1?. Histone PTMs were quantified by mass spectrometry (ChIP-qMS), and their associated DNAs were mapped using deep sequencing. Our results reveal that Brd- and HP1-bound nucleosomes are enriched in histone PTMs consistent with actively transcribed euchromatin and silent heterochromatin, respectively. Data collected using RNA-Seq show that Brd-bound sites correlate with highly expressed genes. In particular, Brd3 and Brd4 are most enriched on nucleosomes located within HOX gene clusters, whose expression is reduced upon Brd4 depletion by short hairpin RNA. CONCLUSIONS:Proteogenomic mapping of histone PTM readers, alongside the characterization of their local chromatin environments and transcriptional information, should prove useful for determining how histone PTMs are bound by these readers and how they contribute to distinct transcriptional states.
| S-EPMC3491368 | biostudies-literature
Project description:Background: Histone post-translational modifications (PTMs) constitute a branch of epigenetic mechanisms that can control the expression of eukaryotic genes in a heritable manner. Recent studies have identified several PTM-binding proteins containing diverse specialized domains whose recognition of specific PTM sites leads to gene activation or repression. Here, we present a high-throughput proteogenomic platform designed to characterize the nucleosomal make-up of chromatin enriched with a set of histone PTM-binding proteins known as histone PTM readers. We support our findings with gene expression data correlating to PTM distribution. Results: We isolated human mononucleosomes bound by the bromodomain-containing proteins Brd2, Brd3 and Brd4, and by the chromodomain-containing heterochromatin proteins HP1alpha and HP1beta. Histone PTMs were quantified by mass spectrometry (ChIP-qMS), and their associated DNAs were mapped using deep sequencing. Our results reveal that Brd- and HP1-bound nucleosomes are enriched in histone PTMs consistent with actively transcribed euchromatin and silent heterochromatin, respectively. Data collected using RNA-Seq (GSM301568) show that Brd-bound sites correlate with highly expressed genes. In particular, Brd3 and Brd4 are most enriched on nucleosomes located within HOX gene clusters, whose expression is reduced upon Brd4 depletion by shRNA. Conclusions: Proteogenomic mapping of histone PTM readers, alongside the characterization of their local chromatin environments and transcriptional information, should prove useful for determining how histone PTMs are bound by these readers and how they contribute to distinct transcriptional states.
2012-07-31 | GSE39580 | GEO
Project description:Background: Histone post-translational modifications (PTMs) constitute a branch of epigenetic mechanisms that can control the expression of eukaryotic genes in a heritable manner. Recent studies have identified several PTM-binding proteins containing diverse specialized domains whose recognition of specific PTM sites leads to gene activation or repression. Here, we present a high-throughput proteogenomic platform designed to characterize the nucleosomal make-up of chromatin enriched with a set of histone PTM-binding proteins known as histone PTM readers. We support our findings with gene expression data correlating to PTM distribution. Results: We isolated human mononucleosomes bound by the bromodomain-containing proteins Brd2, Brd3 and Brd4, and by the chromodomain-containing heterochromatin proteins HP1alpha and HP1beta. Histone PTMs were quantified by mass spectrometry (ChIP-qMS), and their associated DNAs were mapped using deep sequencing. Our results reveal that Brd- and HP1-bound nucleosomes are enriched in histone PTMs consistent with actively transcribed euchromatin and silent heterochromatin, respectively. Data collected using RNA-Seq (GSM301568) show that Brd-bound sites correlate with highly expressed genes. In particular, Brd3 and Brd4 are most enriched on nucleosomes located within HOX gene clusters, whose expression is reduced upon Brd4 depletion by shRNA. Conclusions: Proteogenomic mapping of histone PTM readers, alongside the characterization of their local chromatin environments and transcriptional information, should prove useful for determining how histone PTMs are bound by these readers and how they contribute to distinct transcriptional states. Comparison of Brd2 and HP1b shRNA knockdown HEK293 cells to control knockdown HEK293 cells.
2012-07-30 | E-GEOD-39580 | biostudies-arrayexpress
Project description:Background: Histone post-translational modifications (PTMs) constitute a branch of epigenetic mechanisms that can control the expression of eukaryotic genes in a heritable manner. Recent studies have identified several PTM-binding proteins containing diverse specialized domains whose recognition of specific PTM sites leads to gene activation or repression. Here, we present a high-throughput proteogenomic platform designed to characterize the nucleosomal make-up of chromatin enriched with a set of histone PTM-binding proteins known as histone PTM readers. We support our findings with gene expression data correlating to PTM distribution. Results: We isolated human mononucleosomes bound by the bromodomain-containing proteins Brd2, Brd3 and Brd4, and by the chromodomain-containing heterochromatin proteins HP1alpha and HP1beta. Histone PTMs were quantified by mass spectrometry (ChIP-qMS), and their associated DNAs were mapped using deep sequencing. Our results reveal that Brd- and HP1-bound nucleosomes are enriched in histone PTMs consistent with actively transcribed euchromatin and silent heterochromatin, respectively. Data collected using RNA-Seq (GSM301568) show that Brd-bound sites correlate with highly expressed genes. In particular, Brd3 and Brd4 are most enriched on nucleosomes located within HOX gene clusters, whose expression is reduced upon Brd4 depletion by shRNA. Conclusions: Proteogenomic mapping of histone PTM readers, alongside the characterization of their local chromatin environments and transcriptional information, should prove useful for determining how histone PTMs are bound by these readers and how they contribute to distinct transcriptional states.
2012-07-31 | GSE39579 | GEO
Project description:Background: Histone post-translational modifications (PTMs) constitute a branch of epigenetic mechanisms that can control the expression of eukaryotic genes in a heritable manner. Recent studies have identified several PTM-binding proteins containing diverse specialized domains whose recognition of specific PTM sites leads to gene activation or repression. Here, we present a high-throughput proteogenomic platform designed to characterize the nucleosomal make-up of chromatin enriched with a set of histone PTM-binding proteins known as histone PTM readers. We support our findings with gene expression data correlating to PTM distribution. Results: We isolated human mononucleosomes bound by the bromodomain-containing proteins Brd2, Brd3 and Brd4, and by the chromodomain-containing heterochromatin proteins HP1alpha and HP1beta. Histone PTMs were quantified by mass spectrometry (ChIP-qMS), and their associated DNAs were mapped using deep sequencing. Our results reveal that Brd- and HP1-bound nucleosomes are enriched in histone PTMs consistent with actively transcribed euchromatin and silent heterochromatin, respectively. Data collected using RNA-Seq (GSM301568) show that Brd-bound sites correlate with highly expressed genes. In particular, Brd3 and Brd4 are most enriched on nucleosomes located within HOX gene clusters, whose expression is reduced upon Brd4 depletion by shRNA. Conclusions: Proteogenomic mapping of histone PTM readers, alongside the characterization of their local chromatin environments and transcriptional information, should prove useful for determining how histone PTMs are bound by these readers and how they contribute to distinct transcriptional states. Examination of Brd and HP1 proteins-binding sites in HEK293 cells.
2012-07-31 | E-GEOD-39579 | biostudies-arrayexpress
Project description:Characterization of the genetic regulation of proteins is essential for understanding disease etiology and developing therapies. We identified 10,674 genetic associations for 3892 plasma proteins to create a cis-anchored gene-protein-disease map of 1859 connections that highlights strong cross-disease biological convergence. This proteo-genomic map provides a framework to connect etiologically related diseases, to provide biological context for new or emerging disorders, and to integrate different biological domains to establish mechanisms for known gene-disease links. Our results identify proteo-genomic connections within and between diseases and establish the value of cis-protein variants for annotation of likely causal disease genes at loci identified in genome-wide association studies, thereby addressing a major barrier to experimental validation and clinical translation of genetic discoveries.
| S-EPMC9904207 | biostudies-literature
Project description:Heterochromatin is important for the maintenance of genome stability and regulation of gene expression; yet our knowledge of heterochromatin structure and function is incomplete. We identified four novel Drosophila heterochromatin proteins (HPs). Three of these proteins (HP3, HP4 and HP5) interact directly with HP1, whereas HP6 in turn binds to each of these three proteins. Immunofluorescence microscopy and genome-wide mapping of in vivo binding sites shows that all four proteins are components of heterochromatin. Depletion of HP1 causes redistribution of all four proteins, indicating that HP1 is essential for their heterochromatic targeting. Finally, mutants of HP4 and HP5 are dominant suppressors of position effect variegation, demonstrating their importance in heterochromatic gene silencing. These results indicate that HP1 acts as a docking platform for several mediator proteins that contribute to heterochromatin function.
| S-EPMC1794385 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-03-17 | E-GEOD-75835 | biostudies-arrayexpress
Project description:Primary liver cancer is a heterogeneous disease in terms of its etiology, histology, and therapeutic response. Concurrent proteomic and genomic characterization of a large set of clinical liver cancer samples can help elucidate the molecular basis of heterogeneity and thus serve as a valuable resource for personalized liver cancer treatment. In this study, we perform proteomic profiling of ~300 proteins on 259 primary liver cancer tissues with reverse-phase protein arrays, mutational analysis using whole genome sequencing and transcriptional analysis with RNA-Seq. Patients are of Japanese ethnic background and mainly HBV or HCV positive, providing insight into this important liver cancer subtype. Unsupervised classification of tumors based on protein expression profiles reveal three proteomic subclasses R1, R2, and R3. The R1 subclass is immunologically hot and demonstrated a good prognosis. R2 contains advanced proliferative tumor with TP53 mutations, high expression of VEGF receptor 2 and the worst prognosis. R3 is enriched with CTNNB1 mutations and elevated mTOR signaling pathway activity. Twenty-two proteins, including CDK1 and CDKN2A, are identified as potential prognostic markers. The proteomic classification presented in this study can help guide therapeutic decision making for liver cancer treatment.
| S-EPMC9617926 | biostudies-literature