Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Oncohistone mutations occur at functional sites of regulatory ADP-ribosylation: the role of oncohistone mutations in transcriptional regulation [RNA-Seq]

ABSTRACT: RNA-seq were performed in MDA-MB-231 cells ectopically expressing FLAG-tagged WT, D51A, or D51N H2B, and WT, D68A, or D68N H4

ORGANISM(S): Homo sapiens

PROVIDER: GSE180461 | GEO | 2022/08/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Oncohistone mutations occur at functional sites of regulatory ADP-ribosylation: the role of oncohistone mutations in transcriptional regulation [ATAC-Seq]

Project description:ATAC-seq were performed in MDA-MB-231 cells ectopically expressing FLAG-tagged WT, D51A, or D51N H2B, and WT, D68A, or D68N H4

2022-08-02 | GSE180458 | GEO

Oncohistone mutations occur at functional sites of regulatory ADP-ribosylation: the role of oncohistone mutations in transcriptional regulation [ChIP-Seq]

Project description:H2BK12ac ChIP-seq were performed in MDA-MB-231 cells ectopically expressing FLAG-tagged WT, D51A, or D51N H2B ± treatment with A485 (5 M, 2 hours) or vehicle (DMSO).

2022-08-02 | GSE180459 | GEO

Oncohistone Mutations Occur at Functional Sites of Regulatory ADP-Ribosylation.

Project description:Recent studies have identified cancer-associated mutations in histone genes that lead to the expression of mutant versions of core histones called oncohistones. Many oncohistone mutations occur at Asp and Glu residues, two amino acids known to be ADP-ribosylated (ADPRylated) by PARP1. We screened 25 Glu or Asp oncohistone mutants for their effects on cell growth in breast and ovarian cancer cells. Ectopic expression of six mutants of three different core histones (H2B, H3, and H4) altered cell growth in at least two different cell lines. Two of these sites, H2B-D51 and H4-D68, were indeed sites of ADPRylation in wild-type (unmutated) histones, and mutation of these sites inhibited ADPRylation. Mutation of H2B-D51 dramatically altered chromatin accessibility at enhancers and promoters, as well as gene expression outcomes, whereas mutation of H4-D68 did not. Additional biochemical, cellular, proteomic, and genomic analyses demonstrated that ADPRylation of H2B-D51 inhibits p300-mediated acetylation of H2B at many Lys residues. In breast cancer cell xenografts in mice, H2B-D51A promoted tumor growth, but did not confer resistance to the cytotoxic effects of PARP inhibition. Collectively, these results demonstrate that functional Asp and Glu ADPRylation sites on histones are mutated in cancers, allowing cancer cells to escape the growth-regulating effects of post-translational modifications via distinct mechanisms.SignificanceThis study identifies cancer-driving mutations in histones as sites of PARP1-mediated ADP-ribosylation in breast and ovarian cancers, providing a molecular pathway by which cancers may subvert the growth-regulating effects of PARP1.

| S-EPMC9256803 | biostudies-literature

Oncohistone mutations occur at functional sites of regulatory ADP-ribosylation: the role of oncohistone mutations in transcriptional regulation

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-08-02 | GSE180463 | GEO

Inhibition of Histone H3-H4 Chaperone Pathways Rescues Dysfunctional Oncohistone H2B

Project description:Oncohistone mutations are crucial drivers for tumorigenesis, but how a living organism responds to and governs the loss-of-function oncohistone remains unclear. Here, we generated a histone H2B triple knockout (3KO) strain in Caenorhabditis elegans, which decreased the embryonic H2B level, disrupted cell divisions, and caused animal sterility. Our genetic screens identified mutations defective in a histone H3-H4 chaperone UNC-85 as suppressors that recovered H2B 3KO fertility. We found that unc-85 mutations reduced chromatin H3-H4 levels and that inhibiting other H3-H4 chaperones or H3-H4 histones also rescued H2B 3KO sterility. The oncohistone H2BE76K mutation disrupts the H2B-H4 interface and causes nucleosome instability, and we showed that blocking H3-H4 chaperones restored cell division defects in C. elegans or human cells carrying H2BE76K. Thus, our results indicate that reducing chromatin H3-H4 rescues H2B loss and suggest that inhibiting H3-H4 chaperones may be a therapeutic strategy to treat cancers resulting from loss-of-function H2B oncohistone.

2022-04-03 | GSE185582 | GEO

Oncohistone mutations occur at functional sites of regulatory ADP-ribosylation: the role of oncohistone mutations in transcriptional regulation

Project description:Oncohistone mutations occur at functional sites of regulatory ADP-ribosylation: the role of oncohistone mutations in transcriptional regulation

| PRJNA748361 | ENA

Functional Interplay between Histone H2B ADP-Ribosylation and Phosphorylation Controls Adipogenesis

Project description:Although ADP-ribosylation of histones by PARP-1 has been linked to genotoxic stress responses, its role in physiological processes has remained elusive. We found that ADPribosylation of histone H2B-Glu35 inhibits the differentiation of adipocyte precursors, leading to a reduction of newly formed adipocytes in white adipose tissue. ADP-ribosylation of Glu35 by PARP-1 inhibits phosphorylation of adjacent H2B-Ser36, which is required for the proadipogenic gene expression program. It also inhibits adipogenesis in cultured cells and a mouse lineage tracing genetic model. The activity of PARP-1 on H2B requires NMNAT-1, a nuclear NAD+ synthase, which serves as a specificity factor to direct PARP-1 catalytic activity to Glu and Asp residues. Collectively, our results demonstrate a functional interplay between H2B-Glu35 ADP-ribosylation and H2B-Ser36 phosphorylation that controls adipogenesis and cancer cell proliferation.

2020-08-13 | GSE136055 | GEO

Oncohistone mutations occur at functional sites of regulatory ADP-ribosylation: the role of oncohistone mutations in transcriptional regulation [RNA-Seq]

Project description:Oncohistone mutations occur at functional sites of regulatory ADP-ribosylation: the role of oncohistone mutations in transcriptional regulation [RNA-Seq]

| PRJNA748367 | ENA

Oncohistone mutations occur at functional sites of regulatory ADP-ribosylation: the role of oncohistone mutations in transcriptional regulation [ATAC-Seq]

Project description:Oncohistone mutations occur at functional sites of regulatory ADP-ribosylation: the role of oncohistone mutations in transcriptional regulation [ATAC-Seq]

| PRJNA748363 | ENA

Oncohistone mutations occur at functional sites of regulatory ADP-ribosylation: the role of oncohistone mutations in transcriptional regulation [ChIP-Seq]

Project description:Oncohistone mutations occur at functional sites of regulatory ADP-ribosylation: the role of oncohistone mutations in transcriptional regulation [ChIP-Seq]

| PRJNA748364 | ENA

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data