CHD6 eviction of promoter nucleosomes maintains housekeeping transcriptional program in prostate cancer
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ABSTRACT:
PROVIDER: PRJNA1102338 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Genome-wide binding profile of CHD6 (Bethyl, catalog: A301-221A) in HEK293 were profiled using cleavage under targets and tagmentation sequencing (CUT&Tag-seq).
2024-11-27 | GSE264397 | GEO
Project description:Purpose: Study of the role of CHD6 linking nucleosome ejection in castration-resistant prostate cancer(CRPC) Method: The expression of CHD6 or E2F1 was silenced by 2 shRNAs (3 replicates) targeted at CHD6 or E2F1 in C4-2 cells, scramble RNA as control. mRNA profiles and genome-wide chromatin-state maps were generated by deep sequencing. CHD6 and IgG ChIP was conducted in C4-2 cells. MNase before and after CHD6-silenced was conducted in C4-2 cells. Results: E2F1 and E2F1 downstream genes were significantly down regulated by CHD6 knockdown. The binding of CHD6 on chromatin is required for nucleosome eviction in transcriptional activation of oncogenic pathways.
2022-10-18 | GSE214212 | GEO
Project description:HEK293T cells were transfected with plasmids expressing a control siRNA or a siRNA especific for CHD6 protein. 48H post-transfection, total RNA was isolated and used for transcriptome analysis. Four biological replicates carried out by triplicate were used.
2018-01-31 | GSE109848 | GEO
Project description:Members of the chromodomain-helicase-DNA binding (CHD) protein family are chromatin remodelers implicated in human pathologies, with CHD6 being one of its least studied members. We discovered a de novo CHD6 missense mutation in a patient clinically presenting the rare Hallermann-Streiff syndrome (HSS). We used genome editing to generate isogenic iPSC lines and model HSS in relevant cell types. By combining genomics with functional in vivo and in vitro assays, we show that CHD6 binds a cohort of autophagy and stress response genes across cell types. The HSS mutation affects CHD6 protein folding and impairs its ability to recruit co-remodelers in response to DNA damage or autophagy stimulation. This leads to accumulation of DNA damage burden and senescence-like phenotypes. We therefore uncovered a molecular mechanism explaining HSS onset via chromatin control of autophagic flux and genotoxic stress surveillance.
2021-03-20 | PXD024803 | Pride
Project description:The experiment was performed to assess the importance of nucleosome eviction for the binding of condensin to chromatin during mitosis. The condensin complex associates with chromatin during mitosis to ensure chromosome condensation and accurate segregation, but how this binding is achieved remains poorly understood. Our study indicates that transcription co-activators Gcn5 and Mst2 assist condensin binding during mitosis by evicting nucleosomes. To reach this conclusion, we mapped nucleosomes, during mitosis, in wild-type and gcn5mst2 mutant strains. This experiment allowed us (1) to identify nucleosome-depleted regions (ndrs) during mitosis and to show that condensin tends to colocalize with ndr at the 3ends of genes, and (2) to confirm the importance of nucleosome eviction from ndrs by gcn5 and mst2, during mitosis, for the binding of condensin to chromatin.this experiment determines the patterns of nucleosomes in wild type and mutant fission yeast cells arrested in early mitosis. We analysed wild-type cells, cells lacking Gcn5 histone acetylatransferase (gcn5D) and cells lacking both Gcn5 and Mst2 histone acetyltransferases (Gcn5Dmst2D). All cells used in this study expressed a GFP-tagged version of condensin (Cnd2-GFP) and were blocked in early mitosis at 19C by the nda3-KM311 mutation. Mitotic indexes were determined by scoring the accumulation of Cnd2-GFP in the nucleus. Mitotic cells were collected and chromatin was digested by increasing amount of MNase to produce mononucleosomes. Mononucleosomal DNA was purified on an agarose gel and sequence on an Illumina Nextseq 500 apparatus. Three replicates of wild type, gcn5D and gcn5Dmst2D were analysed. Nucleosome patterns were determined in wild-type cells, cells lacking Gcn5 and cells lacking both Gcn5 and Mst2.
2016-04-18 | E-MTAB-4620 | biostudies-arrayexpress
Project description:How various ATP-dependent chromatin remodellers bind to nucleosomes to regulate transcription is not well defined in mammalian cells. Here, we present genome-wide remodeller-interacting nucleosome profiles for Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1 and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind to nucleosomes at specific positions, either at one or both nucleosomes that flank each side of nucleosome-free promoter regions (NFRs), at enhancer elements, or within gene bodies. At promoters, bidirectional transcription commonly initiates on either side of remodeller-bound nucleosomes. Transcriptome analysis upon remodeller depletion reveals reciprocal mechanisms of transcriptional regulation by remodellers. At active genes, certain remodellers are positive regulators of transcription, whereas others act as repressors. At bivalent genes, which are bound by repressive Polycomb complexes, the same remodellers act in the opposite way. Together, these findings reveal how remodellers integrate promoter nucleosomal architecture to regulate ES cell transcription programs.
2016-01-26 | GSE64782 | GEO
Project description:Despite being a member of the chromodomain helicase DNA-binding protein family, little is known about the exact role of CHD6 in chromatin remodeling or cancer disease. Here we show that CHD6 binds to chromatin to promote broad nucleosome eviction for transcriptional activation of many cancer pathways. By integrating multiple patient cohorts for bioinformatics analysis of over a thousand prostate cancer datasets, we found CHD6 expression elevated in prostate cancer and associated with poor prognosis. Further comprehensive experiments demonstrated that CHD6 regulates oncogenicity of prostate cancer cells and tumor development in a murine xenograft model. ChIP-Seq for CHD6, along with MNase-Seq and RNA-Seq, revealed that CHD6 binds on chromatin to evict nucleosomes from promoters and gene bodies for transcriptional activation of oncogenic pathways. These results demonstrated a key function of CHD6 in evicting nucleosomes from chromatin for transcriptional activation of prostate cancer pathways.
| S-EPMC9757051 | biostudies-literature
Project description:Colorectal cancer is one of the most common cancers. Cancer cells are highly dependent on dysregulated gene expression to support their uncontrolled growth and high energy needs. The expression of gene encoding chromodomain helicase DNA binding protein 6 (CHD6) is frequently altered in tumor tissues of colorectal cancer patients.We performed transcriptomic analysis to identify the differentially expressed genes between control and CHD6 KD HCT116.
2022-12-14 | GSE163124 | GEO
Project description:Members of the Chromodomain-Helicase-DNA binding (CHD) protein family are chromatin remodelers critically implicated in human pathologies. CHD6 is the least studied member of this family, and we were motivated to dissect its in-cell roles by discovering a mutated CHD6 allele in a patient suffering from the rare Hallermann-Streiff premature aging syndrome (HSS). We generated isogenic iPSC lines carrying (or not) this single point mutation in the CHD6 SANT/SLIDE domain, which allow studying HSS-relevant cell identities. Using these lines, we show for the first time that CHD6 binds the promoters of a cohort of autophagy and stress response genes across cell types. This CHD6 mutation impairs its ability to recruit co-factors and regulate genes in response to DNA damage and autophagy stimulation, thus leading to accumulation of unresolved DNA damage burden. By combining genomics and functional assays, we describe a molecular mechanism underlying chromatin control of autophagic flux and genotoxic stress surveillance that is broadly applicable to human cell types and can explain HSS establishment.
2021-02-19 | GSE136057 | GEO