Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA197337 | ENA |
REPOSITORIES: ENA
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Project description:Chromatin-to-nucleoprotamine transition is controlled by the histone H2B variant TH2B [ChIP-Seq]
| PRJNA196684 | ENA
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: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.
2013-10-18 | GSE45915 | 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
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: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: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:Histones scaffold genomic DNA and regulate access to the transcriptional machinery. However, naturally occurring histone variants can alter histone-DNA interactions, DNA and histone modifications, and the chromatin interactome. Hence, alterations in histone variant deposition can disrupt chromatin, and are increasingly recognized as a way to trigger various disease (including cancer). While significant attention has been placed on the biochemical and functional roles of H2A and H3 variants, H2B variants remain largely understudied. Here, we show that H2B variants are dysregulated in breast cancer and that certain variants are associated with specific breast cancer subtypes. HIST1H2BO overexpression (in particular) is more common in Asian, African American/Black, and young female populations and is associated with a worse prognosis. In vitro, H2B1O compacts chromatin, and incorporating H2B1O into chromatin activates pro-inflammatory and oncogenic pathways and the epithelial-to-mesenchymal transition (EMT), and generates resistance to first-line chemotherapeutic agents. Thus, H2B1O acts much like an onco-histone, with H2B variant expression being a prognostic biomarker for breast cancer and a potential new target for drug therapies to enhance treatment efficacy.
2026-02-11 | GSE285390 | GEO
Project description:Histones scaffold genomic DNA and regulate access to the transcriptional machinery. However, naturally occurring histone variants can alter histone-DNA interactions, DNA and histone modifications, and the chromatin interactome. Hence, alterations in histone variant deposition can disrupt chromatin, and are increasingly recognized as a way to trigger various disease (including cancer). While significant attention has been placed on the biochemical and functional roles of H2A and H3 variants, H2B variants remain largely understudied. Here, we show that H2B variants are dysregulated in breast cancer and that certain variants are associated with specific breast cancer subtypes. HIST1H2BO overexpression (in particular) is more common in Asian, African American/Black, and young female populations and is associated with a worse prognosis. In vitro, H2B1O compacts chromatin, and incorporating H2B1O into chromatin activates pro-inflammatory and oncogenic pathways and the epithelial-to-mesenchymal transition (EMT), and generates resistance to first-line chemotherapeutic agents. Thus, H2B1O acts much like an onco-histone, with H2B variant expression being a prognostic biomarker for breast cancer and a potential new target for drug therapies to enhance treatment efficacy.
2026-02-11 | GSE285389 | GEO