Mus musculus
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ABSTRACT:
PROVIDER: PRJNA232529 | ENA |
REPOSITORIES: ENA
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Project description:Expression of key transcription factors Klf4, Oct3/4, Sox2, and c-Myc (KOSM) in embryonic stem cells can reprogram somatic cells into pluripotent cells. We found that two histone variants, TH2A and TH2B, and histone chaperone Npm enhance the KOSM-dependent generation of induced pluripotent cells (iPSCs) and produce iPSCs only with Klf4 and Oct3/4. To identify directly affected genes by these histone variants during reprogramming, we carried out gene expression profiling of MEFs overexpressing TH2A/TH2B/Npm and TH2A/TH2B deficient MEFs after infection with retroviruses expressing KOSM. A total of 21 Affymetrix Mouse Gene ST array were done for mRNA expression profiling of ES cells, iPS cells induced by Klf4, Oct4, Sox2, and c-Myc (KOSM) or Klf4, Oct4, Th2a, Th2b, and p-Npm (KOBAN), wild-type MEFs infected with retrovirus vectors expressing KOSM, KOSMBAN, or empty vector and Th2a/Th2b-deficient MEFs infected with retrovirus vector expressing KOSM.
2013-12-25 | E-GEOD-53637 | biostudies-arrayexpress
Project description:Expression of key transcription factors Klf4, Oct3/4, Sox2, and c-Myc (KOSM) in embryonic stem cells can reprogram somatic cells into pluripotent cells. We found that two histone variants, TH2A and TH2B, and histone chaperone Npm enhance the KOSM-dependent generation of induced pluripotent cells (iPSCs) and produce iPSCs only with Klf4 and Oct3/4. To identify directly affected genes by these histone variants during reprogramming, we carried out gene expression profiling of MEFs overexpressing TH2A/TH2B/Npm and TH2A/TH2B deficient MEFs after infection with retroviruses expressing KOSM.
2013-12-25 | GSE53637 | 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:In this study, chromatin immunoprecipitated sequencing was done for testis specific histone variants of H2B and H2A, TH2B and TH2A to understand the epigenomics of these retained histones, using murine caudal sperm.Our in silico analysis has attributed a myriad of novel functions to sperm retained TH2B with respect to embryo development and spermatogenesis.Also, based on genomic regions, TH2B was observed to be associated with spindle assembly and various meiosis-specific genes, which is an important finding as TH2A/TH2B DKO mice have been reported to have defective cohesin release.We also observed a degree of evolutionary conservation between the TH2B-DNA linkage across human and mouse.This overlap included genes important for embryogenesis. Most importantly, heterogeneity in the epigenetic landscape of TH2A and TH2B was seen which is intriguing as TH2B and TH2A are well reported to be present in the same nucleosomes to promote open chromatin. Additionally, unlike TH2B, TH2A was enriched on the mitochondrial chromosome. We presume that TH2A is associated with mitochondrial DNA inserted in the nuclear DNA and this observation needs further validation.. A comprehensive analysis of these observations indicates novel functions for the sperm retained TH2B and TH2A.
2021-12-06 | GSE181921 | GEO
Project description:The testis-specific histone variant of H2B, TH2B, is enriched in the oocytes, sperm and early embryos, with levels decreasing as the embryos differentiate into pre-gastrula stages. However, the involvement of TH2B in epigenetic reprogramming in the preimplantation embryos is largely unknown. The current study mapped the genome-wide epigenetics of TH2B in MII oocytes and early embryos using ultra-low-input ChIP-seq (ULI-ChIP). We demonstrate that TH2B deposition varies greatly between gametes; however, following fertilization, TH2B from gametes is swiftly redistributed in 2-cell embryos. A considerable enrichment of TH2B at the transcription start site (TSS) was identified in sperm chromatin compared to that in oocytes. We also found some overlap between the dynamics of the sperm and the 2 cell, which contain genes related to transcription regulation. Additionally, TH2B was enriched at zygotic genome activation (ZGA) genes. H2A.Z and TH2B were associated, as was discovered in the presence of H2AK119ub1. The correct execution of ZGA and other developmental programs, such as timing the expression or repression of particular genes, may involve TH2B along with H2A.Z, and H2AK119ub1, the latter two regulating the aforementioned processes. Also, early embryos had H3K9me3 deposited at TH2B-bound loci, which is a sign of heterochromatin and functions in regulating retrotransposons. In our study, we found that TH2B was enriched in LTRs. Thus, TH2B chromatin in gametes and preimplantation embryos has distinctive properties, as highlighted by our study, and they also present fresh opportunities to investigate the epigenetic dynamics in murine preimplantation embryos.
2024-08-31 | GSE243322 | GEO
Project description:The conversion of male germ cell chromatin to a nucleoprotamine structure is fundamental to the life cycle yet the underlying molecular details remain obscure. Here we show that an essential step is the genome-wide incorporation of TH2B, a histone H2B variant of hitherto unknown function. Using mouse models in which TH2B is depleted or C-terminally modified we show that TH2B directs the final transformation of dissociating nucleosomes into protamine-packed structures. Depletion of TH2B induces compensatory mechanisms that permit histone removal by up-regulating H2B and programming nucleosome instability through targeted histone modifications, including lysine crotonylation and arginine methylation. Furthermore, after fertilization, TH2B re-assembles onto the male genome during protamine-to-histone exchange. Thus, TH2B is a unique histone variant, which plays a key role in the histone-to-protamine packing of the male genome and guides genome-wide chromatin transitions that both precede and follow transmission of the male genome to the egg. Examination of TH2B binding on chromatin in meiotic (spermatocytes) and post-meiotic (round spermatids) male germ cells from adult Th2b+/tag mice (TH2B C-terminally fused to three consecutive affinity tags: His, Flag and Ha). Examination of TH2B (wild type) binding on chromatin in male germ cells from adult wt mice.
2013-10-18 | E-GEOD-45915 | biostudies-arrayexpress
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:The conversion of male germ cell chromatin to a nucleoprotamine structure is fundamental to the life cycle yet the underlying molecular details remain obscure. Here we show that an essential step is the genome-wide incorporation of TH2B, a histone H2B variant of hitherto unknown function. Using mouse models in which TH2B is depleted or C-terminally modified we show that TH2B directs the final transformation of dissociating nucleosomes into protamine-packed structures. Depletion of TH2B induces compensatory mechanisms that permit histone removal by up-regulating H2B and programming nucleosome instability through targeted histone modifications, including lysine crotonylation and arginine methylation. Furthermore, after fertilization, TH2B re-assembles onto the male genome during protamine-to-histone exchange. Thus, TH2B is a unique histone variant, which plays a key role in the histone-to-protamine packing of the male genome and guides genome-wide chromatin transitions that both precede and follow transmission of the male genome to the egg. Total RNA were obtained from testes from meiotic (spermatocytes) and post-meiotic (round spermatids) male germ cells from adult wt and Th2b+/tag mice (experiment 1: 6 biological replicates for each condition) and adult wt and th2bkd mice (experiment 2: 5 biological replicates for each condition). In each experiment, 5 or 6 replicates of each genotype and each cell type were used. Th2b+/tag mice expressed TH2B C-terminally fused to three consecutive affinity tags: His, Flag and Ha. Th2bkd mice did not express any TH2B.
2013-10-17 | E-GEOD-46136 | biostudies-arrayexpress
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:The conversion of male germ cell chromatin to a nucleoprotamine structure is fundamental to the life cycle yet the underlying molecular details remain obscure. Here we show that an essential step is the genome-wide incorporation of TH2B, a histone H2B variant of hitherto unknown function. Using mouse models in which TH2B is depleted or C-terminally modified we show that TH2B directs the final transformation of dissociating nucleosomes into protamine-packed structures. Depletion of TH2B induces compensatory mechanisms that permit histone removal by up-regulating H2B and programming nucleosome instability through targeted histone modifications, including lysine crotonylation and arginine methylation. Furthermore, after fertilization, TH2B re-assembles onto the male genome during protamine-to-histone exchange. Thus, TH2B is a unique histone variant, which plays a key role in the histone-to-protamine packing of the male genome and guides genome-wide chromatin transitions that both precede and follow transmission of the male genome to the egg.
2013-10-17 | GSE46136 | GEO