Cell-cycle-dependent repression of histone gene transcription by histone H4
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens Drosophila melanogaster
PROVIDER: GSE280833 | GEO | 2025/11/11
REPOSITORIES: GEO
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Project description:The histone locus body (HLB) assembles at replication-dependent (RD) histone loci and concentrates factors required for RD histone mRNA biosynthesis. The D. melanogaster genome has a single locus comprised of ~100 copies of a tandemly arrayed 5 kB repeat unit containing one copy of each of the 5 RD histone genes. To determine sequence elements required for D. melanogaster HLB formation and histone gene expression, we used transgenic gene arrays containing 12 copies of the histone repeat unit that functionally complement loss of the ~200 endogenous RD histone genes. A 12x histone gene array in which all H3-H4 promoters were replaced with H2a-H2b promoters (12xPR) does not form an HLB or express high levels of RD histone mRNA in the presence of the endogenous histone genes. In contrast, this same transgenic array is active in HLB assembly and RD histone gene expression in the absence of the endogenous RD histone genes and rescues the lethality caused by homozygous deletion of the RD histone locus. The HLB formed in the absence of endogenous RD histone genes on the mutant 12x array contains all known factors present in the wild type HLB including CLAMP, which normally binds to GAGA repeats in the H3-H4 promoter. These data suggest that multiple protein-protein and/or protein-DNA interactions contribute to HLB formation, and that the large number of endogenous RD histone gene copies sequester available factor(s) from attenuated transgenic arrays, thereby preventing HLB formation and gene expression. ChIP-qPCR and ChIP-Seq experiments were done on homozygous histone locus (HisC) deletion embryos rescued by the 12 copy promoter replacement (PR) or designer wild type (DWT) arrays on the third chromosome (VK33) to determine CLAMP's interaction with the locus
2020-05-12 | GSE150297 | GEO
Project description:The conserved histone locus body (HLB) assembles prior to zygotic gene activation early during development and concentrates factors into a nuclear domain of coordinated histone gene regulation. Although HLBs form specifically at replication dependent histone loci, the cis and trans factors that target HLB components to histone genes remained unknown. Here we report that conserved GA-repeat cis elements within the bidirectional histone3-histone4 promoter direct HLB formation in Drosophila. In addition, the CLAMP zinc-finger protein binds these GA-repeat motifs, increases chromatin accessibility, enhances histone gene transcription, and promotes HLB formation. We previously demonstrated that CLAMP also promotes the formation of another domain of coordinated gene regulation: the dosage-compensated male X-chromosome. Therefore, CLAMP binding to GA-repeat motifs promotes the formation of two distinct domains of coordinated gene activation located at different places in the genome.
2017-11-15 | GSE102922 | GEO
Project description:The conserved histone locus body (HLB) assembles prior to zygotic gene activation early during development and concentrates factors into a nuclear domain of coordinated histone gene regulation. Although HLBs form specifically at replication-dependent histone loci, the cis and trans factors that target HLB components to histone genes remained unknown. Here we report that conserved GA repeat cis elements within the bidirectional histone3-histone4 promoter direct HLB formation in Drosophila In addition, the CLAMP (chromatin-linked adaptor for male-specific lethal [MSL] proteins) zinc finger protein binds these GA repeat motifs, increases chromatin accessibility, enhances histone gene transcription, and promotes HLB formation. We demonstrated previously that CLAMP also promotes the formation of another domain of coordinated gene regulation: the dosage-compensated male X chromosome. Therefore, CLAMP binding to GA repeat motifs promotes the formation of two distinct domains of coordinated gene activation located at different places in the genome.
2018-09-05 | GSE119448 | GEO
Project description:Importins could inhibit the condensation of RNA-binding proteins, while it is proposed that exportins could not elicit a similar function. Here, we identified exportin CRM1 binds nuclear protein NPAT, which initiates and maintains the formation of histone locus body (HLB), a membrane-less nuclear body determining histone transcription. CRM1 drives the nuclear export of NPAT by targeting a cryptical nuclear export signal (NES) motif within the LisH domain. The LisH domain contributes to NPAT condensation by mediating its self-association. Mechanistically, CRM1 competitively occupies the self-association sites in the NES motif to suppress NPAT condensation. In contrast, the two recurrent CRM1 E571K and E571G mutants could not regulate NPAT condensation and HLB remodeling due to their impaired binding to the NES of NPAT. Based on the “competitive occupation” model, we designed a LisH domain-derived short peptide that competes with homotypic intermolecular interactions of NPAT to perturb HLB formation. Our findings reveal that exportin regulates nuclear protein condensation via a “competitive occupation” strategy.
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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
Project description:Histones are pivotal carriers of epigenetic information through post-translational modifications (PTMs), crucial for regulating gene expression, proper cellular function and maintaining cell identity. Perturbations in histone levels within the aging genome can profoundly impact chromatin structure and gene expression profiles. In this study, we examined the effects of age-related changes on histone levels and histone acetylation in the retinal pigment epithelium (RPE) and retina of mice. Our findings revealed a global reduction in histones H1, H2A, H2B, H3, and H4 within the aged RPE/choroid, while the neural retina remained unaffected. Transcriptome analysis unveiled a significant downregulation of histone genes in the aged RPE/choroid, including key components of the histone locus body (HLB) complex involved in histone pre-mRNA processing. Knockdown of HINFP, a critical HLB component, in human RPE cells resulted in histone loss, induction of senescence, and upregulation of senescence-associated secretory phenotype (SASP) markers. Replicative aging of human RPE cells exhibited progressive histone loss and acquisition of the SASP phenotype. Immunostaining of human retina sections demonstrated a gradual decline in histones within the aging RPE. Additionally, aging in mice RPE/choroid led to diminished global histone acetylation levels, particularly H3K14ac, H3K56ac, and H4K16ac marks. These alterations in histone acetylation were metabolically driven and correlated with changes in acetyl-CoA abundance. Collectively, our findings highlight the characteristic loss of histones as a hallmark of aging in the RPE/choroid, shedding light on potential mechanisms linking histone dynamics, cellular senescence, and age-related functional changes in RPE cells.
2023-07-15 | GSE236220 | GEO
Project description:Histones are pivotal carriers of epigenetic information through post-translational modifications (PTMs), crucial for regulating gene expression, proper cellular function and maintaining cell identity. Perturbations in histone levels within the aging genome can profoundly impact chromatin structure and gene expression profiles. In this study, we examined the effects of age-related changes on histone levels and histone acetylation in the retinal pigment epithelium (RPE) and retina of mice. Our findings revealed a global reduction in histones H1, H2A, H2B, H3, and H4 within the aged RPE/choroid, while the neural retina remained unaffected. Transcriptome analysis unveiled a significant downregulation of histone genes in the aged RPE/choroid, including key components of the histone locus body (HLB) complex involved in histone pre-mRNA processing. Knockdown of HINFP, a critical HLB component, in human RPE cells resulted in histone loss, induction of senescence, and upregulation of senescence-associated secretory phenotype (SASP) markers. Replicative aging of human RPE cells exhibited progressive histone loss and acquisition of the SASP phenotype. Immunostaining of human retina sections demonstrated a gradual decline in histones within the aging RPE. Additionally, aging in mice RPE/choroid led to diminished global histone acetylation levels, particularly H3K14ac, H3K56ac, and H4K16ac marks. These alterations in histone acetylation were metabolically driven and correlated with changes in acetyl-CoA abundance. Collectively, our findings highlight the characteristic loss of histones as a hallmark of aging in the RPE/choroid, shedding light on potential mechanisms linking histone dynamics, cellular senescence, and age-related functional changes in RPE cells.
2023-07-15 | GSE236219 | GEO
Project description:Histone turnover during DNA replication
| PRJNA794181 | ENA
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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To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL5954483266 | BioModels
Project description:How parental histone H3-H4 tetramers, the primary carrier of epigenetic modifications, are transferred to leading and lagging strands of DNA replication forks following DNA replication is an important question that remains not well understood. Here we show that DNA polymerase clamp PCNA and its partner involved in lagging strand DNA synthesis, Pol d, regulate parental histone transfer to lagging strands. Mutations at PCNA as well as at subunits of Pol d that impair the PCNA-Pol d interaction affect parental histone transfer to lagging strands, and this defect unlikely arises from their impacts on DNA synthesis. Moreover, Pol d interacts with H3-H4 in vitro. We suggest that the PCNA-Pol d complex, best known for its role in lagging strand DNA synthesis and DNA repair, couples lagging strand DNA synthesis to the transfer of the parental histones H3-H4 for the inheritance of chromatin structures following DNA replication and possibly DNA repair.
2024-05-31 | GSE203465 | GEO