UBR7 Acts as a Chaperone for Post-Nucleosomal Histone H3
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ABSTRACT:
PROVIDER: PRJNA761773 | ENA |
REPOSITORIES: ENA
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Project description:Histone chaperones modulate the stability of histones beginning from histone synthesis, through incorporation into DNA, and during recycling during transcription and replication. Following histone removal from DNA, chaperones regulate histone storage and degradation. Here we characterize UBR7 as a histone H3.1 chaperone that modulates the supply of pre-existing post-nucleosomal histone complexes. UBR7 is a largely nuclear soluble protein. We demonstrate that UBR7 binds to post-nucleosomal H3K4me3 and H3K9me3 histones via its UBR box and PHD. UBR7 binds to the non-nucleosomal histone chaperone NASP. The pool of NASP-bound post-nucleosomal histones accumulate and chromatin is depleted of H3K4me3 nucleosomes in the absence of UBR7. We propose that the interaction of UBR7, NASP, and histones opposes the histone storage functions of NASP as UBR7 promotes reincorporation of post-nucleosomal H3 complexes.
2021-12-02 | GSE183730 | GEO
Project description: Not available
| S-SCDT-EMBOJ-2021-108307 | biostudies-other
Project description:Histones are essential for chromatin packaging and histone supply must be tightly regulated as excess histones are toxic. To drive the rapid cell cycles of the early embryo, however, excess histones are maternally deposited. Therefore, soluble histones must be buffered by histone chaperones but the chaperone necessary to stabilize soluble H3-H4 pools in the Drosophila embryo has yet to be identified. Here, we show that CG8223, the Drosophila ortholog of NASP, is a H3-H4-specific chaperone in the early embryo. NASP specifically binds to H3-H4 in the early embryo. We demonstrate that, while NASP is non-essential in Drosophila, NASP is maternal effect lethal gene. Embryos laid by NASP mutant mothers have a reduce rate of hatching and show defects in early embryogenesis. Critically, soluble H3-H4 pools are degraded in embryos laid by NASP mutant mothers. Our work identifies NASP as the critical H3-H4 histone chaperone in the Drosophila embryo.
2023-02-23 | PXD036809 | Pride
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:Mislocalization of CENP-A to non-centromeric regions contributes to chromosomal instability (CIN). Here, we defined a role for the histone H3/H4 chaperone CHAF1B in preventing mislocalization of CENP-A and CIN.
2023-05-05 | GSE227373 | GEO
Project description:Inhibition of Histone H3-H4 Chaperone Pathways Rescues Dysfunctional Oncohistone H2B
| PRJNA769715 | ENA
Project description:Nucleosomal incorporation of specialized histone variants is an important mechanism to generate different functional chromatin states. Here we report the identification and characterization of two novel primate-specific histone H3 variants, H3.X and H3.Y. Their mRNAs are found in certain human cell lines, in addition to several normal and malignant human tissues. In keeping with their primate-specificity, H3.X and H3.Y are detected in different brain regions. Transgenic H3.X and H3.Y proteins are stably incorporated into chromatin in a similar fashion to the known H3 variants. Importantly, we demonstrate biochemically and by mass spectrometry that endogenous posttranslationally modified H3.Y protein exists in vivo, and that stress-stimuli, such as starvation and cellular density, increase the abundance of H3.Y-expressing cells. Global transcriptome analysis revealed that knock-down of H3.Y affects cell growth and leads to changes in the expression of many genes involved in cell cycle control. Thus, H3.Y is a novel histone variant involved in the regulation of cellular responses to outside stimuli. Total RNA samples from human U2OS cells. Transcript levels after luciferase, H3.X and/or H3.Y RNAi was analyzed.
2010-09-17 | E-GEOD-22415 | biostudies-arrayexpress
Project description:Nucleosomal incorporation of specialized histone variants is an important mechanism to generate different functional chromatin states. Here we report the identification and characterization of two novel primate-specific histone H3 variants, H3.X and H3.Y. Their mRNAs are found in certain human cell lines, in addition to several normal and malignant human tissues. In keeping with their primate-specificity, H3.X and H3.Y are detected in different brain regions. Transgenic H3.X and H3.Y proteins are stably incorporated into chromatin in a similar fashion to the known H3 variants. Importantly, we demonstrate biochemically and by mass spectrometry that endogenous posttranslationally modified H3.Y protein exists in vivo, and that stress-stimuli, such as starvation and cellular density, increase the abundance of H3.Y-expressing cells. Global transcriptome analysis revealed that knock-down of H3.Y affects cell growth and leads to changes in the expression of many genes involved in cell cycle control. Thus, H3.Y is a novel histone variant involved in the regulation of cellular responses to outside stimuli.
2010-09-17 | GSE22415 | GEO
Project description:From biosynthesis to assembly into nucleosomes, histones are handed through a cascade of histone chaperones, which shield histones from non-specific interactions. Whether mechanisms exist to safeguard the histone fold during histone chaperone handover events or to release trapped intermediates is unclear. Using structure-guided and functional proteomics, we identify and characterize a histone chaperone function of DNAJC9, a heat shock co-chaperone that promotes HSP70-mediated catalysis. We elucidate the structure of DNAJC9, in a histone H3-H4 co-chaperone complex with MCM2, revealing how this dual histone and heat shock co-chaperone binds histone substrates. We show that DNAJC9 recruits HSP70-type enzymes via its J domain to fold histone H3-H4 substrates: upstream in the histone supply chain, during replication- and transcription-coupled nucleosome assembly, and to clean up spurious interactions. With its dual functionality, DNAJC9 integrates ATP-resourced protein folding into the histone supply pathway to resolve aberrant intermediates throughout the dynamic lives of histones.
2021-04-14 | GSE154445 | GEO
Project description:Chaperones, nucleosome remodeling complexes and histone acetyltransferases have been implicated in nucleosome disassembly at promoters of particular yeast genes, but whether these co-factors function ubiquitously, and the impact of nucleosome eviction on transcription genome-wide, are poorly understood. We used chromatin immunoprecipitation of histone H3 and RNA polymerase II (Pol II) in mutants lacking single or multiple co-factors to address these issues for ~200 genes belonging to the Gcn4 transcriptome, of which ~70 exhibit marked reductions in H3 promoter occupancy on induction by amino acid starvation. Examining four target genes in a panel of mutants indicated that SWI/SNF, Gcn5, the Hsp70 co-chaperone Ydj1, and chromatin-associated factor Yta7 are required downstream of Gcn4 binding for robust H3 eviction in otherwise wild-type cells. Using ChIP-seq to interrogate all 70 exemplar genes in single, double and triple mutants implicated Gcn5, Snf2 and Ydj1 in H3 eviction at most, but not all Gcn4 target promoters, with Gcn5 generally playing the greatest role and Ydj1 the least. Remarkably, these 3 co-factors cooperate similarly in H3 eviction at virtually all yeast promoters. Defective H3 eviction in co-factor mutants was coupled with reduced Pol II occupancies for the Gcn4 transcriptome and the most highly expressed uninduced genes, but the relative Pol II levels at most genes were unaffected or even elevated. These findings indicate that nucleosome eviction is crucial for robust transcription of highly expressed genes, but that other steps in gene activation are more rate-limiting for most other yeast genes. Chromatin immunoprecipitated DNA from WT (induced(+SM) and uninduced(no SM)) and mutants (induced(+SM)) followed by paired-end sequencing. Nucleosomal DNA obtained by MNase digestion were also subjected to paired-end sequencing.
2015-11-09 | E-GEOD-74787 | biostudies-arrayexpress