Histone H3 proline 16 hydroxylation regulates mammalian gene expression [CUT&RUN]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE179108 | GEO | 2022/08/02
REPOSITORIES: GEO
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Project description:Histone posttranslational modifications (PTMs) are important for regulating various DNA-templated processes. Emerging evidence suggests a critical involvement of the previously less-explored histone PTMs in gene activity regulation. Here, we report the existence of a new histone PTM in the mammalian cells, hydroxylation of H3 proline 16 (H3P16-OH) catalyzed by EglN2, a proline hydroxylase. We show that EglN2-mediated H3P16-OH enhances direct binding of Lysine-Specific Demethylase 5A (KDM5A) with its substrate, H3 lysine 4 trimethylation (H3K4me3), resulting in enhanced chromatin recruitment of KDM5A and decrease of H3K4me3 at target genes. Genome-wide mapping by CUT&RUN in multiple mammalian cell models reveals a functional connection between EglN2, H3P16-OH, KDM5A and H3K4me3. Integrated analysis with RNA-Seq also identifies distinct subsets of genes that are regulated through H3P16-OH in different cell lines. This study therefore demonstrates a new player of the “histone code” by revealing a role of H3P16-OH in regulating gene expression in mammalian cells.
2022-08-02 | GSE179112 | GEO
Project description:KDM5A encodes a histone lysine demethylase that removes methyl groups from lysine 4 of histone H3, resulting in repression of target genes. In order to identify KDM5A targets, we profiled transcripts from hippocampi of WT and Kdm5a -/- mice. Loss of KDM5A resulted in dysregulation of 450 genes (FDR-corrected P ≤0.05 and log2 fold change ≥|0.3|), of which 191 genes were upregulated and 259 genes were downregulated.
2020-12-14 | GSE147435 | GEO
Project description:Both genetic and environmental factors are implicated in Type 1 Diabetes (T1D). Since environmental factors can trigger epigenetic changes, we hypothesized that variations in histone posttranslational modifications (PTMs) at the promoter/enhancer regions of T1D susceptible genes may be associated with T1D. We therefore evaluated histone PTM variations at known T1D susceptible genes in blood cells from T1D patients versus healthy non-diabetic controls, and explored their connections to T1D. We used the chromatin-immunoprecipitation-linked-to-microarray approach to profile key histone PTMs, including H3-lysine-4 trimethylation (H3K4me3), H3K27me3, H3K9me3, H3K9 acetylation (H3K9Ac) and H4K16Ac at genes within the T1D susceptible loci in lymphocytes, and H3K4me3, H3K9me2, H3K9Ac and H4K16Ac at the IDDM1 region in monocytes of T1D patients and healthy controls separately. We screened for potential variations in histone PTMs using computational methods to compare datasets from T1D and controls. Interestingly, we observed marked variations in H3K9Ac levels at the upstream regions of HLA-DRB1 and HLA-DQB1 within the IDDM1 locus in T1D monocytes relative to controls. Additional experiments with THP-1 monocytes demonstrated increased expression of HLA-DRB1 and HLA-DQB1 in response to interferon- and TNF-treatment that were accompanied by changes in H3K9Ac at the same promoter regions as that seen in the patient monocytes. These results suggest that the H3K9Ac status of HLA-DRB1 and HLA-DQB1, two genes highly associated with T1D, may be relevant to their regulation and transcriptional response towards external stimuli. Thus, the promoter/enhancer architecture and chromatin status of key susceptible loci could be important determinants in their functional association to T1D susceptibility. We used ChIP-chip to profile key histone PTMs, including H3K4me3, H3K9me2, H3K9Ac and H4K16Ac, at the IDDM1 region in monocytes of T1D patients and healthy controls.
2012-05-31 | E-GEOD-36397 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE10836: Meiotic time course of Histone H3 occupancy GSE10837: Meiotic time course of the trimethylation of the Lysine 4 of Histone H3 (H3K4me3) in a mutant Spo11F GSE10838: Meiotic time course of Histone H3 occupancy in a mutant Spo11F GSE10839: Meiotic time course of the trimethylation of the Lysine 4 of Histone H3 (H3K4me3) in a mutant clb5Delta-clb6Delta GSE10840: Meiotic time course of the trimethylation of the Lysine 4 of Histone H3 (H3K4me3) GSE10944: Transcriptomic regulation during meiosis GSE10947: Transcriptomic regulation during meiosis (Spo11Y135F mutant) GSE10948: Transcriptomic regulation during meiosis (Clb5Delta-Clb6Delta mutant) GSE12879: Meiotic DNA double strand breaks in wild-type and set1 cells Keywords: SuperSeries Refer to individual Series
2008-10-31 | E-GEOD-11004 | biostudies-arrayexpress
Project description:Both genetic and environmental factors are implicated in Type 1 Diabetes (T1D). Since environmental factors can trigger epigenetic changes, we hypothesized that variations in histone posttranslational modifications (PTMs) at the promoter/enhancer regions of T1D susceptible genes may be associated with T1D. We therefore evaluated histone PTM variations at known T1D susceptible genes in blood cells from T1D patients versus healthy non-diabetic controls, and explored their connections to T1D. We used the chromatin-immunoprecipitation-linked-to-microarray approach to profile key histone PTMs, including H3-lysine-4 trimethylation (H3K4me3), H3K27me3, H3K9me3, H3K9 acetylation (H3K9Ac) and H4K16Ac at genes within the T1D susceptible loci in lymphocytes, and H3K4me3, H3K9me2, H3K9Ac and H4K16Ac at the IDDM1 region in monocytes of T1D patients and healthy controls separately. We screened for potential variations in histone PTMs using computational methods to compare datasets from T1D and controls. Interestingly, we observed marked variations in H3K9Ac levels at the upstream regions of HLA-DRB1 and HLA-DQB1 within the IDDM1 locus in T1D monocytes relative to controls. Additional experiments with THP-1 monocytes demonstrated increased expression of HLA-DRB1 and HLA-DQB1 in response to interferon- and TNF-treatment that were accompanied by changes in H3K9Ac at the same promoter regions as that seen in the patient monocytes. These results suggest that the H3K9Ac status of HLA-DRB1 and HLA-DQB1, two genes highly associated with T1D, may be relevant to their regulation and transcriptional response towards external stimuli. Thus, the promoter/enhancer architecture and chromatin status of key susceptible loci could be important determinants in their functional association to T1D susceptibility. We evaluated histone PTM variations at known T1D susceptible genes in blood cells from T1D patients versus healthy non-diabetic controls, and explored their connections to T1D. We used the ChIP-chip approach to profile key histone PTMs, including histone H3K4me3, H3K27me3, H3K9me3, H3K9 acetylation (H3K9Ac) and H4K16Ac, at genes within the T1D susceptible loci in lymphocytes.
2012-05-31 | E-GEOD-36402 | biostudies-arrayexpress
Project description:Tri-methylation on histone H3 lysine 4 (H3K4me3) is enriched near transcription start sites and correlates with active transcription. Like other histone marks, methylation on H3K4 is catalyzed by the respective methyltransferases and erased by demethylases. Lysine demethylase 5 (KDM5) family of Fe (II) and α-ketoglutarate-dependent dioxygenases removes the methyl groups from H3K4me3. All four family members of KDM5 demethylases (KDM5A-D) share sequence identity, have similar in vitro kinetic parameters, and display functional redundancy. To determine the effects of complete depletion of KDM5 activity, we treated MCF7 cells with DMSO, or two pan-KDM5 specific inhibitors, KDM5-C70 (our lab code 443) and CPI-48 (our lab code 278) and performed RNA sequencing to determine gene expression changes after KDM5 inhibitor treatment.
2018-07-03 | GSE108502 | GEO
Project description:The menin tumor suppressor protein (Men1) is deficient in many endocrine tumors and forms an active complex with MLL family histone methyltransferases. This Men1 complex promotes histone H3 lysine 4 trimethylation at target loci including homeobox genes and cyclin-dependent kinase inhibitor genes. The loss of Men1 may be tumorigenic because it leads to decreased histone H3 lysine 4 trimethylation resulting in expressional changes of specific genes. Reversing tumorigenesis induced by a Men1 deficiency might be achieved by inhibition of histone H3 lysine 4 demethylase Rbp2 (Kdm5a). To this end, pancreatic islets from Men1f|f, Rbp2f|f and Men1f|f Rbp2f|f mice were expression profiled to determine what transcriptional changes induced by a Men1 deficiency are reversed by the loss of Rpb2. Pancreatic islets were isolated from Men1flf RIP-Cre mice, Rbp2flf RIP-Cre mice, Men1flf Rbp2flf RIP-Cre mice and two month old matched control mice. Total mRNA was extracted from islets and expression profiled on microarrays.
2011-07-25 | E-GEOD-26978 | biostudies-arrayexpress
Project description:The menin tumor suppressor protein (Men1) is deficient in many endocrine tumors and forms an active complex with MLL family histone methyltransferases. This Men1 complex promotes histone H3 lysine 4 trimethylation at target loci including homeobox genes and cyclin-dependent kinase inhibitor genes. The loss of Men1 may be tumorigenic because it leads to decreased histone H3 lysine 4 trimethylation resulting in expressional changes of specific genes. Reversing tumorigenesis induced by a Men1 deficiency might be achieved by inhibition of histone H3 lysine 4 demethylase Rbp2 (Kdm5a). To this end, pancreatic islets from Men1f|f, Rbp2f|f and Men1f|f Rbp2f|f mice were expression profiled to determine what transcriptional changes induced by a Men1 deficiency are reversed by the loss of Rpb2.
2011-07-26 | GSE26978 | GEO
Project description:This model is described in the article:
Kinetics of histone gene expression during early development of Xenopus laevis.
Koster JG, Destrée OH and Westerhoff HV. J Theor Biol.
1988 Nov 21;135(2):139-67. PMID: 3267765
Abstract:
Using literature data for transcriptional and translational rate constants, gene copy numbers, DNA concentrations, and stability constants, we have calculated the expected concentrations of histones and histone mRNA during embryogenesis of Xenopus laevis. The results led us to conclude that: (i) for X. laevis the gene copy number of the histone genes is too low to ensure the synthesis of sufficient histones during very early development, inheritance from the oocyte of either histone protein or histone mRNA (but not necessarily both) is necessary; (ii) from the known storage of histones in the oocyte and the rates of histone synthesis determined by Adamson and Woodland (1977), there would be sufficient histones to structure the newly synthesized DNA up to gastrulation but not thereafter (these empirical rates of histone synthesis may be underestimates); (iii) on the other hand, the amount of H3 mRNA recently observed during early embryogenesis (Koster, 1987, Koster et al., 1988) could direct a higher and sufficient synthesis of H3 protein, also after gastrulation. We present a quantitative model that accounts both for the observed H3 mRNA concentration as a function of time during embryogenesis and for the synthesis of sufficient histones to structure the DNA throughout early embryogenesis. The model suggests that X. laevis exhibits a major (i.e. some 14-fold) reduction in transcription of histone genes approximately 11 hours after fertilization. This reduction could be due to a decrease in the number of transcribed histone genes, a decreased rate constant of transcription with continued transcription of all the histone genes, and/or a reduction in the time during the cell cycle in which histone mRNA synthesis takes place. Alternatively, the histone mRNA stability might decrease approximately 16-fold 11 hours after fertilization.
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2005-01-01 | MODEL5954483266 | BioModels
Project description:we performed chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq) to profile histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 acetylation (H3K27ac) in pituitary gland of adult Bama Xiang and Large White pigs with divergent evolutionary histories and large phenotypic differences.
2021-06-18 | GSE178380 | GEO