Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA245895 | ENA |
REPOSITORIES: ENA
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Project description:Functional Roles of Acetylated Histone Marks at Mouse Meiotic Recombination Hotspots (sequencing)
| PRJNA343463 | ENA
Project description:Functional Roles of Acetylated Histone Marks at Mouse Meiotic Recombination Hotspots
| PRJNA343465 | ENA
Project description:Meiotic recombination is initiated by the Spo11 endonuclease, which directs DNA DSBs. We report here that the recombinogenic cores of active hotspots in mice harbor several histone H3 and H4 acetylation and methylation marks that are typical of open, active chromatin. Further, deposition of these histone marks is dynamic and manifest at spermatogonia and/or pre-leptotene meiotic cells, which would facilitate the formation of DSBs at leptotene. Importantly, there was concordance in the overlap of the histone mark ChIP profiles with nucleosome occupancy maps, which were determined by real-time PCR and whole genome sequencing (WGS) analyses of micococcal-nuclease resistance regions across four mouse meiotic hotspots (HS22, HS59.4, HS59.5 and HS61.1). Our study reveals that there are instructive roles of histone acetylated marks at meiotic recombination hotspot cores and that they are necessary to promote hotspot activity and crossover resolution.
2016-11-04 | GSE87057 | GEO
Project description:Meiotic recombination ensures proper chromosome segregation and genetic diversity during gametogenesis, and its disruption leads to infertility. It is known that the dual histone methylation writer–reader system, in which PRDM9 deposits H3K4me3 and H3K36me3 marks at nucleosomes to specify recombination hotspots and ZCWPW1 functions as a reader recognizing these marks, is essential for meiotic recombination. However, the regulatory mechanism of this system remains unclear. Here, Deficiency of ZCWPW2 causes recombination defects, with impairment in homologous synapsis and DNA double-strand break repair. CUT&Tag and mass spectrometry analyses revealed that ZCWPW2 recognizes PRDM9-mediated dual histone methylation and interacts with ZCWPW1 to form a complex that recruits recombination-associated proteins to hotspots. Additionally, ZCWPW2 independently binds to promoter regions to regulate meiotic transcription. Lactylome and proteome analyses demonstrated that the ZCWPW1–ZCWPW2 complex interacts with and maintains the activity of lactate dehydrogenase LDHA, and together with ZCWPW2-driven transcription of lactylation writer EP300, to promote lactylation of recombination-associated proteins and stabilize their expression at hotspots. Collectively, we identified ZCWPW2 as a previously unrecognized yet indispensable factor supporting the function of PRDM9/ZCWPW1 during meiotic recombination, elucidated the molecular mechanism of the PRDM9/ZCWPW1/ZCWPW2 system in regulating recombination, and uncovered a critical role for lactylation in meiosis.
2026-01-07 | PXD068838 | Pride
Project description:Meiotic recombination ensures proper chromosome segregation and genetic diversity during gametogenesis, and its disruption leads to infertility. It is known that the dual histone methylation writer–reader system, in which PRDM9 deposits H3K4me3 and H3K36me3 marks at nucleosomes to specify recombination hotspots and ZCWPW1 functions as a reader recognizing these marks, is essential for meiotic recombination. However, the regulatory mechanism of this system remains unclear. Here, Deficiency of ZCWPW2 causes recombination defects, with impairment in homologous synapsis and DNA double-strand break repair. CUT&Tag and mass spectrometry analyses revealed that ZCWPW2 recognizes PRDM9-mediated dual histone methylation and interacts with ZCWPW1 to form a complex that recruits recombination-associated proteins to hotspots. Additionally, ZCWPW2 independently binds to promoter regions to regulate meiotic transcription. Lactylome and proteome analyses demonstrated that the ZCWPW1–ZCWPW2 complex interacts with and maintains the activity of lactate dehydrogenase LDHA, and together with ZCWPW2-driven transcription of lactylation writer EP300, to promote lactylation of recombination-associated proteins and stabilize their expression at hotspots. Collectively, we identified ZCWPW2 as a previously unrecognized yet indispensable factor supporting the function of PRDM9/ZCWPW1 during meiotic recombination, elucidated the molecular mechanism of the PRDM9/ZCWPW1/ZCWPW2 system in regulating recombination, and uncovered a critical role for lactylation in meiosis.
2026-01-07 | PXD070427 | Pride
Project description:Histone modifications are associated with meiotic recombination hotspots, discrete sites with augmented recombination frequency. For example, trimethylation of histone H3 lysine4 (H3K4me3) marks most hotspots in budding yeast and mouse. Modified histones are known to regulate meiotic recombination partly by promoting DNA double strand break (DSB) formation, but the role and precise landscape of histone modifications at hotspots remain unclear. Here, we studied hotspot-associated modifications in fission yeast and found general features: acetylation of H3 lysine9 (H3K9ac) is strikingly elevated, and H3K4me3 is not significantly enriched. Remarkably, elimination of H3K9ac reduced binding of the DSB-inducing enzyme Rec12 and DSB at hotspots. We also found that the H3K4 metyltransferase Set1 promotes DSB formation at some loci, but it restricts Rec12 binding to hotspots. These results suggest that H3K9ac rather than H3K4me3 is a hotspot-associated mark involved in meiotic DSB formation in fission yeast.
2013-03-07 | GSE31648 | GEO
Project description:Histone modifications are associated with meiotic recombination hotspots, discrete sites with augmented recombination frequency. For example, trimethylation of histone H3 lysine4 (H3K4me3) marks most hotspots in budding yeast and mouse. Modified histones are known to regulate meiotic recombination partly by promoting DNA double strand break (DSB) formation, but the role and precise landscape of histone modifications at hotspots remain unclear. Here, we studied hotspot-associated modifications in fission yeast and found general features: acetylation of H3 lysine9 (H3K9ac) is strikingly elevated, and H3K4me3 is not significantly enriched. Remarkably, elimination of H3K9ac reduced binding of the DSB-inducing enzyme Rec12 and DSB at hotspots. We also found that the H3K4 metyltransferase Set1 promotes DSB formation at some loci, but it restricts Rec12 binding to hotspots. These results suggest that H3K9ac rather than H3K4me3 is a hotspot-associated mark involved in meiotic DSB formation in fission yeast. S.pombe cells in a pat1-114 background were induced to enter meiosis by the haploid meiosis system, and harvested one hour after the induction. ChIP were performed using anti-H3Cter, H3K9ac, -H3K14ac and -H3K4me3 antibodies. pat1-114 rad50S rec12+-FLAG cells in a wild type, H3K9A or set1+ deletion background were induced to enter meiosis by the haploid meiosis system, and harvested five hours after the induction. ChIP were performed using anti-FLAG antibodies.
2013-03-07 | E-GEOD-31648 | biostudies-arrayexpress
Project description:Meiotic recombination is initiated by the Spo11 endonuclease, which directs DNA double strand breaks at discrete regions in the genome coined hotspots. Here we report the profiles and dynamics of histone modifications at the cores of mouse recombination hotspots in early meiotic prophase. To define the spectrum of possible regulators of histone methylation and acetylation at all stages of meiosis I, expression analyses of histone acetylases/deacetylases (HATs/HDACs) and and HMTs/HDMTs genes when comparing those expressed in spermatogonia, pre-leptotene and leptotene/zygotene versus pachytene meiotic stages.
2016-11-04 | GSE57197 | GEO
Project description:Meiotic recombination hotspots are associated with histone post-translational modifications and open chromatin. However, it remains unclear how histone modifications and chromatin structure directly regulate meiotic recombination. Here, we identify acetylation of histone H4 at Lys44 (H4K44ac) as a new histone modification, occurring on the nucleosomal lateral surface. We show that H4K44ac is specific to yeast sporulation, rising during yeast meiosis and displaying genome-wide enrichment at recombination hotspots in meiosis. The H4K44 residue is required for normal meiotic recombination, for normal levels of double strand breaks during meiosis, and for optimal sporulation. Non-modifiable substitution H4K44R results in reduced MNase digestion and decreased binding of recombination-associated proteins at hotspots. Our results show that H4K44ac creates an accessible chromatin environment for key proteins to facilitate meiotic recombination.
2015-12-07 | GSE59004 | GEO
Project description:Meiotic recombination hotspots are associated with histone post-translational modifications and open chromatin. However, it remains unclear how histone modifications and chromatin structure directly regulate meiotic recombination. Here, we identify acetylation of histone H4 at Lys44 (H4K44ac) as a new histone modification, occurring on the nucleosomal lateral surface. We show that H4K44ac is specific to yeast sporulation, rising during yeast meiosis and displaying genome-wide enrichment at recombination hotspots in meiosis. The H4K44 residue is required for normal meiotic recombination, for normal levels of double strand breaks during meiosis, and for optimal sporulation. Non-modifiable substitution H4K44R results in reduced MNase digestion and decreased binding of recombination-associated proteins at hotspots. Our results show that H4K44ac creates an accessible chromatin environment for key proteins to facilitate meiotic recombination.
2015-12-07 | GSE59003 | GEO