TH2BS11ph histone mark is enriched in the unsynapsed axes of the XY body and predominantly associates with H3K4me3-containing genomic regions in mammalian spermatocytes
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ABSTRACT:
PROVIDER: PRJNA557723 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9877284_1.fastq.gz | Fastqsanger.gz | |||
| SRR9877284_2.fastq.gz | Fastqsanger.gz | |||
| SRR9877285_1.fastq.gz | Fastqsanger.gz | |||
| SRR9877285_2.fastq.gz | Fastqsanger.gz | |||
| SRR9877286.fastq.gz | Fastqsanger.gz |
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Project description:BACKGROUND:TH2B is a major histone variant that replaces about 80-85% of somatic H2B in mammalian spermatocytes and spermatids. The post-translational modifications (PTMs) on TH2B have been well characterised in spermatocytes and spermatids. However, the biological function(s) of these PTMs on TH2B have not been deciphered in great detail. In our attempt to decipher the unique function(s) of histone variant TH2B, we detected the modification in the N-terminal tail, Serine 11 phosphorylation on TH2B (TH2BS11ph) in spermatocytes. RESULTS:The current study is aimed at understanding the function of the TH2BS11ph modification in the context of processes that occur during meiotic prophase I. Immunofluorescence studies with the highly specific antibodies revealed that TH2BS11ph histone mark is enriched in the unsynapsed axes of the sex body and is associated with XY body-associated proteins like Scp3, γH2AX, pATM, ATR, etc. Genome-wide occupancy studies as determined by ChIP sequencing experiments in P20 C57BL6 mouse testicular cells revealed that TH2BS11ph is enriched in X and Y chromosomes confirming the immunofluorescence staining pattern in the pachytene spermatocytes. Apart from the localisation of this modification in the XY body, TH2BS11ph is majorly associated with H3K4me3-containing genomic regions like gene promoters, etc. These data were also found to corroborate with the ChIP sequencing data of TH2BS11ph histone mark carried out in P12 C57BL6 mouse testicular cells, wherein we found the predominant localisation of this modification at H3K4me3-containing genomic regions. Mass spectrometry analysis of proteins that associate with TH2BS11ph-containing mononucleosomes revealed key proteins linked with the functions of XY body, pericentric heterochromatin and transcription. CONCLUSIONS:TH2BS11ph modification is densely localised in the unsynapsed axes of the XY body of the pachytene spermatocyte. By ChIP sequencing studies in mouse P12 and P20 testicular cells, we demonstrate that TH2BS11ph is predominantly associated with H3K4me3 positive genomic regions like gene promoters, etc. We propose that TH2BS11ph modification could act alone or in concert with other histone modifications to recruit the appropriate transcription or XY body recombination protein machinery at specific genomic loci.
| S-EPMC6731575 | biostudies-literature
Project description:In mammals and several other taxa, the ability of males to cope with the limited synapsis of the X and Y chromosomes during prophase I of meiosis relies on the process of meiotic sex chromosome inactivation (MSCI). Components of the somatic DNA damage response machinery, including ATR, TOPBP1, MDC1 and BRCA1 play key roles in MSCI, although how they establish XY silencing remains incompletely understood. In particular, it remains unclear how DDR factors coordinate XY silencing with DNA repair, chromosome synapsis and the formation of the sex body, a distinct phase-separated sub-nuclear structure formed during prophase I to house the unsynapsed XY bivalent. Here we report a mutant mouse (Topbp1B5/B5), harboring mutations in the BRCT5 domain of Topbp1, that shows impaired XY silencing but grossly normal sex body formation. While Topbp1B5/B5 mice are viable, without detectable somatic defects, males are completely infertile. Distinct from mice lacking ATR or TOPBP1 specifically during meiosis, Topbp1B5/B5 males exhibit normal chromosome synapsis and canonical markers of DNA repair in early prophase I. ATR signaling is mostly intact in Topbp1B5/B5 spermatocytes, although specific ATR-dependent events are disrupted, including localization of the RNA:DNA helicase Senataxin to chromatin loops of the XY. Strikingly, while Topbp1B5/B5 spermatocytes are able to initiate MSCI the completion of gene silencing is defective, with a subset of X chromosome genes displaying distinct patterns of transcriptional deregulation. These findings suggest a non-canonical role for the ATR-TOPBP1 signaling axis in XY silencing dynamics at advanced stages in pachynema. This is the first DDR mutant that separates XY silencing from sex body formation, as well as TOPBP1’s role in spermatogenesis from its roles in organismal viability.
2024-02-09 | PXD042199 | Pride
Project description:We report the localisation of TH2BS11ph histone mark in leptotene and pachytene cells determined by ChIP sequencing analysis
2019-09-15 | GSE135209 | GEO
Project description:In the testis of the mice, most spermatogonia are in pachytene stage. We have harvested spermatogonia from 3-week-old mice. As γH2AX is the marker of the XY body, we performed RNA-seq following RNA-ChIP using anti-γH2AX antibody in germ cells to report the γH2AX associated RNA in mouse spermatocytes, while IgG as the negative control. Process of RNA-ChIP for germ cells was as the ChIP protocol with some modifications.
2021-09-26 | GSE184711 | GEO
Project description:Background: The ubiquitin-conjugating enzyme HR6B is required for spermatogenesis in mouse. Loss of HR6B results in aberrant histone modification patterns on the trancriptionally silenced X and Y chromosomes (XY body) and on centromeric chromatin in meiotic prophase. We studied the relationship between these chromatin modifications and their effects on global gene expression patterns, in spermatocytes and spermatids. Results: HR6B is enriched on the XY body and on centromeric regions in pachytene spermatocytes. Global gene expression analyses revealed that spermatid-specific single- and multicopy X-linked genes are prematurely expressed in Hr6b knockout spermatocytes. Very few other differences in gene expression were observed in these cells, except for upregulation of major satellite repeat transcription. In contrast, in Hr6b knockout spermatids, 7298 genes were differentially expressed; 65% of these genes was downregulated, but we observed a global upregulation of gene transcription from the X chromosome. In wildtype spermatids, approximately 20% of the single-copy X-linked genes reach an average expression level that is similar to the average expression from autosomes. Conclusions: Spermatids maintain an enrichment of repressive chromatin marks on the X chromosome, originating from meiotic prophase, but this does not interfere with transcription of the single-copy X-linked genes that are reactivated or specifically activated in spermatids. HR6B represses major satellite repeat transcription in spermatocytes, and functions in the maintenance of X chromosome silencing in spermatocytes and spermatids. It is discussed that these functions involve modification of chromatin structure, possibly including H2B ubiquitylation. 8 Affymetrix microarrays were generated: 4 from wildtype and HR6B knockout spermatocytes (2 replicates each), and 4 from wildtype and HR6B knockout spermatids (2 replicates each).
2010-05-27 | E-GEOD-21749 | biostudies-arrayexpress
Project description:Background: The ubiquitin-conjugating enzyme HR6B is required for spermatogenesis in mouse. Loss of HR6B results in aberrant histone modification patterns on the trancriptionally silenced X and Y chromosomes (XY body) and on centromeric chromatin in meiotic prophase. We studied the relationship between these chromatin modifications and their effects on global gene expression patterns, in spermatocytes and spermatids. Results: HR6B is enriched on the XY body and on centromeric regions in pachytene spermatocytes. Global gene expression analyses revealed that spermatid-specific single- and multicopy X-linked genes are prematurely expressed in Hr6b knockout spermatocytes. Very few other differences in gene expression were observed in these cells, except for upregulation of major satellite repeat transcription. In contrast, in Hr6b knockout spermatids, 7298 genes were differentially expressed; 65% of these genes was downregulated, but we observed a global upregulation of gene transcription from the X chromosome. In wildtype spermatids, approximately 20% of the single-copy X-linked genes reach an average expression level that is similar to the average expression from autosomes. Conclusions: Spermatids maintain an enrichment of repressive chromatin marks on the X chromosome, originating from meiotic prophase, but this does not interfere with transcription of the single-copy X-linked genes that are reactivated or specifically activated in spermatids. HR6B represses major satellite repeat transcription in spermatocytes, and functions in the maintenance of X chromosome silencing in spermatocytes and spermatids. It is discussed that these functions involve modification of chromatin structure, possibly including H2B ubiquitylation.
2010-05-08 | GSE21749 | GEO
Project description:This dataset contains fibroblasts from different genital and extragenital regions, mostly from 46,XY individuals. Due to proven androgen receptor gene mutations, several individuals have varying degrees of undervirilization of the external genitalia ranging from complete androgen insensitivity syndrome (CAIS) to partial androgen insensitivity syndrome (PAIS). CAIS is a completely female person despite a 46,XY karyotype. AIS-3 individuals have ambigous external genitalia. AIS-4 means predominantly female (clitoral enlargement), AIS-2 means predominantly male (hypospadias). It is important for this experiment set, that it contains data from 3 differet independent datasets that are not directly cmparable with each other. This is because of different reference RNAs and different glass slides. The particular normalization procedure is described in the paper accompanying this dataset. Only then, all arrays are allowed to be clustered together. Dataset 2 and 3 have "DS-2" and "DS-3" in their experiment names. All other experiments belong to dataset 1. A cell type comparison design experiment design type compares cells of different type for example different cell lines. Disease State: normal male, normal female or ambiguous external genitalia according to grading scheme by Sinnecker et al. Cell Line: fibroblast cell lines from different regions of the genital skin, some from extragenital skin Sex/Mating type: 46,XY or 46,XX karyotype Computed
2010-06-25 | E-GEOD-6796 | biostudies-arrayexpress
Project description:This dataset contains fibroblasts from different genital and extragenital regions, mostly from 46,XY individuals. Due to proven androgen receptor gene mutations, several individuals have varying degrees of undervirilization of the external genitalia ranging from complete androgen insensitivity syndrome (CAIS) to partial androgen insensitivity syndrome (PAIS). CAIS is a completely female person despite a 46,XY karyotype. AIS-3 individuals have ambigous external genitalia. AIS-4 means predominantly female (clitoral enlargement), AIS-2 means predominantly male (hypospadias). It is important for this experiment set, that it contains data from 3 differet independent datasets that are not directly cmparable with each other. This is because of different reference RNAs and different glass slides. The particular normalization procedure is described in the paper accompanying this dataset. Only then, all arrays are allowed to be clustered together. Dataset 2 and 3 have "DS-2" and "DS-3" in their experiment names. All other experiments belong to dataset 1. A cell type comparison design experiment design type compares cells of different type for example different cell lines. Disease State: normal male, normal female or ambiguous external genitalia according to grading scheme by Sinnecker et al. Cell Line: fibroblast cell lines from different regions of the genital skin, some from extragenital skin Sex/Mating type: 46,XY or 46,XX karyotype Keywords: cell_type_comparison_design
2007-10-20 | GSE6796 | GEO
Project description:Ubiquitylation of histones provides an important mechanism regulating chromatin remodeling and gene expression. Recent studies have revealed ubiquitin ligases involved in histone ubiquitylation, yet the responsible enzymes and the function of histone ubiquitination in spermatogenesis remain unclear. Here we show that the ubiquitin ligase UBR2, one of the recognition E3 components of the N-end rule proteolytic pathway, localizes to meiotic chromatin regions, including unsynapsed axial elements linked to chromatin inactivation, and mediates, in combination with the ubiquitin-conjugating enzyme HR6B, the ubiquitination of histone H2A. UBR2 interacts with HR6B and H2A and promotes the HR6B-H2A interaction and the HR6B-to-H2A transfer of ubiquitin. UBR2 and ubiquitinated H2A (uH2A) spatiotemporally mark meiotic chromatin regions subject to transcriptional silencing, and UBR2-deficient spermatocytes fail to induce the ubiquitination of H2A during meiosis. UBR2-deficient spermatocytes are profoundly impaired in transcriptional silencing of genes linked to unsynapsed axes of the X and Y chromosomes. We propose a model, in which UBR2 on axial elements of the X-Y pair enables HR6B on the linked chromatin domain to repeat histone ubiquitination cycles while scanning a string of nucleosomes. Our results suggest that histone ubiquitination in germ cells may be mediated by E3-E2 pairs distinct from those in somatic cells, providing a new insight into chromatin remodeling and gene expression regulation. For each genotype, 2 testes were collected from different individual in same litter at 17 days old. Biotinylated cRNA was produced and hybridized on Affimetrix mouse genome 430A 2.0 array.
2010-03-03 | E-GEOD-18824 | biostudies-arrayexpress
Project description:Abdominal aortic aneurysms (AAAs) are a prevalent and deadly human pathology with strong sexual dimorphism. Research demonstrates that sex hormones influence, but do not fully explain, male versus female AAA pathology. In addition to sex hormones, the X and Y sex chromosomes, and their unique complements of genes, may contribute to sexually dimorphic AAA pathology. Here, for the first time, we defined the effect of female (XX) versus male (XY) chromosome complement on AAA formation and rupture in phenotypically female mice using an established murine model. Abdominal aortas from female mice bearing the XY chromosome selectively expressed Y chromosome genes, while genes known to escape X-inactivation were higher in XX females. The majority of gene differences in XY females fell within inflammatory pathways. When XY females were infused with AngII, AAA incidences doubled and aneurysms ruptured. AAAs from XY females exhibited significant inflammation. Moreover, infusion of AngII to XY females augmented aortic activity of matrix metalloproteinases. Finally, testosterone exposure applied chronically, or as a single bolus at postnatal day 1, markedly worsened AAA outcomes in XY compared to XX females. These results demonstrate that an XY sex chromosome complement profoundly influences aortic gene expression profiles and promotes AAA severity.
2016-11-07 | GSE81580 | GEO