Transcriptomic analysis of the effect of histone H4 K31R mutation in U2OS cells
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ABSTRACT:
PROVIDER: PRJNA521963 | ENA |
REPOSITORIES: ENA
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Project description:To explore the genome-wide gene expression changes induced by the K31R mutation in the histone H4 protein, we performed RNA-sequencing analysis in U2OS cells expressing either wildtype H4 or K31R mutant H4. We found that the lysine (K) to arginine (R) mutation mainly affected oxidative phosphorylation, mtiochondria dysfunction and et al, but not DNA damage signaling pathways.
2019-02-20 | GSE126451 | GEO
Project description:Nucleosome structure directly influences gene transcription. However, the function of each histone residue remains largely unknown. Here we profiled gene expression changes upon the mutation of individual residues of histone H3 and H4. Histone residues grouped by expression change similarity displayed overall structural relevance. This regulatory functional map of the core histones led to novel findings. First, the residues specific to each histone family tend to be more influential than those commonly found among different histones. Second, unlike histone acetylations, H3K4 trimethylation does not appear to be prerequisite for gene activation. Third, H3Q5 has been newly identified for its putative interactions with many chromatin regulators for transcription control. Lastly, the nucleosome lateral surface seems to play a key role through interactions with the surrounding DNA. Remarkably, we discovered a novel role for H3K56 in chromatin dynamics. The deletion of this residue, but not the alteration of acetylation states, caused a genome-wide decrease in nucleosome mobility and stabilized nucleosome positioning near transcription start and end sites. Occupying the DNA entry/exit site, H3K56 is thought to modulate nucleosome sliding along DNA. Taken together, genomics approaches such as microarray and deep sequencing prove valuable for mapping the function of histone residues. Microarray analysis was performed for 123 histone mutants and four wild-types as two reaplications of H3 and H4 of Saccharomyces ceravisiae.
2012-12-05 | E-GEOD-29059 | biostudies-arrayexpress
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
Project description:To study the role of Histone H4 lysine 20 mono- and tri-methylation (H4K20me1, H4K20me3) in relationship to chromatin accessibility and gene expression, we report the application of high-throughput profiling of these marks in Human Osteosarcoma U2OS and Mouse Fibroblast (MEF) cells with Set8 knockdown or control siRNA treatment. We find that H4K20me1 contributes to the open chromatin structure at active genes.
2021-06-04 | GSE156216 | GEO
Project description:Total RNA samples from three replicate cultures of wild type and mutant yeast strains was isolated and expression profile done using Affymetrix arrays. Comparsion between the samples indicate how mutation in a single amino acid residue in histone H4 (H4R45H) affects gene expression in yeast. Such a mutation in histone H4 is known to generate a specific class of mutants called SWI/SNF independent (SIN) mutants, and the mutants were identified by their ability to carry out transcription in the absence of yeast chromatin remodeling complex SWI/SNF. SIN mutations are known to affect higher order chromatin structure and the comparative expression profile would help identification of genes which get affected by such altered chromatin landscape. Experiment Overall Design: Comparison of genes whose mRNA levels are affected in histone H4R45H mutant yeast strains compared to wild type yeast strain WY139. This comparison reveals how subtle change in a single amino acid residue in core domain of histone H4 affects gene expression profile in yeast.
2008-10-20 | E-GEOD-11282 | biostudies-arrayexpress
Project description:To study the role of Histone H4 lysine 20 mono- and tri-methylation (H4K20me1, H4K20me3) in relationship to chromatin accessibility and gene expression, we report the application of high-throughput profiling of these marks in synchronized and asynchronous Human Osteosarcoma U2OS and asynchronous Mouse Fibroblast (MEF) cells with Set8 knockdown or control siRNA treatment. We find that H4K20me1 contributes to the open chromatin structure at active genes.
2021-06-04 | GSE173313 | GEO
Project description:To study the role of Histone H4 lysine 20 mono- and tri-methylation (H4K20me1, H4K20me3) in relationship to chromatin accessibility and gene expression, we report the application of high-throughput profiling of these marks in synchronized and asynchronous Human Osteosarcoma U2OS and asynchronous Mouse Fibroblast (MEF) cells with Set8 knockdown or control siRNA treatment. We find that H4K20me1 contributes to the open chromatin structure at active genes.
2021-06-04 | GSE156215 | GEO
Project description:A series of yeast carrying K->R mutations in the histone H4 N-terminal tail were profiled by gene expression array in mid-log phase.
2010-06-10 | E-GEOD-2324 | biostudies-arrayexpress
Project description:Core histone proteins collected from normal human dermal fibroblasts were
separated using a 2-dimensional reverse phase hydrophilic interaction liquid
chromatography (RP-HILIC) system. Histone H4 isolated in the first dimension of
the separation was analyzed using an LTQ Orbitrap Velos with a resolution of 60k
for MS and MS/MS spectra. In total, 1,626 CID and 1,626 ETD spectra were
acquired.
2018-02-11 | MSV000082054 | MassIVE
Project description:Histone chaperones and chromatin remodelers control nucleosome dynamics, essential for transcription, replication, and DNA repair. The histone chaperone Anti-Silencing Factor 1 (ASF1) plays a central role in facilitating CAF-1-mediated replication-dependent H3.1 deposition and HIRA-mediated replication-independent H3.3 deposition in yeast and metazoans. Whether ASF1 function is evolutionarily conserved in plants is unknown. Here, we show that Arabidopsis ASF1 proteins display an exclusive preference for the H3.3-depositing HIRA complex. Simultaneous mutation of both Arabidopsis ASF1 genes caused a decrease in chromatin density and ectopic H3.1 occupancy at loci typically enriched with H3.3. Genetic, transcriptomic, and proteomic data indicate that ASF1 proteins strongly prefer the HIRA complex over CAF-1. asf1 mutants also displayed an increase in spurious Pol II transcriptional initiation, and showed defects in the maintenance of gene body CG DNA methylation and in the distribution of histone modifications. Furthermore, ectopic targeting of ASF1 caused excessive histone deposition, less accessible chromatin, and gene silencing. These findings reveal the importance of ASF1-mediated H3.3-H4 deposition via the HIRA pathway for proper epigenetic regulation of the genome.
2022-10-31 | PXD035578 | Pride