Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA385893 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5515760.fastq.gz | Fastqsanger.gz | |||
| SRR5515761.fastq.gz | Fastqsanger.gz | |||
| SRR5515758.fastq.gz | Fastqsanger.gz | |||
| SRR5515759.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
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Project description:The deacetylase activity of histone deacetylase 3 is required for productive VDJ recombination and B cell development
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Project description:The deacetylase activity of histone deacetylase 3 is required for productive VDJ recombination and B cell development [ATAC-seq]
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Project description:Histone deacetylase 3 (HDAC3) is the catalytic component of NCoR/SMRT corepressor complexes that mediate the actions of transcription factors implicated in the regulation of B cell development and function. We crossed Hdac3 conditional knockout mice with Mb1-Cre knockin animals to delete Hdac3 in early progenitor B cells. The spleens of Hdac3F/-Mb1-Cre+/- mice were virtually devoid of mature B cells, and B220+CD43+ B cell progenitors accumulated within the bone marrow. Quantitative deep sequencing of the immunoglobulin heavy chain locus from B220+CD43+ populations identified a defect in VHDJH recombination with a severe reduction in productive rearrangements, which directly corresponded to the loss of pre-B cells from Hdac3D/- bone marrow. For Hdac3D/- B cells that did show productive VDJ rearrangement, there was significant skewing toward the incorporation of proximal VH gene segments and a corresponding reduction in distal VH gene segment usage. While transcriptional effects within these loci were modest, Hdac3D/- progenitor cells displayed global changes in chromatin structure that likely hindered effective distal V-DJ recombination. Re-introduction of wild type Hdac3 restored normal B cell development, whereas an Hdac3 point mutant lacking deacetylase activity failed to complement this defect. Thus, the deacetylase activity of Hdac3 is required for the generation of mature B cells.
2017-06-05 | GSE98650 | GEO
Project description:Histone deacetylase 3 (HDAC3) is the catalytic component of NCoR/SMRT corepressor complexes that mediate the actions of transcription factors implicated in the regulation of B cell development and function. We crossed Hdac3 conditional knockout mice with Mb1-Cre knockin animals to delete Hdac3 in early progenitor B cells. The spleens of Hdac3F/-Mb1-Cre+/- mice were virtually devoid of mature B cells, and B220+CD43+ B cell progenitors accumulated within the bone marrow. Quantitative deep sequencing of the immunoglobulin heavy chain locus from B220+CD43+ populations identified a defect in VHDJH recombination with a severe reduction in productive rearrangements, which directly corresponded to the loss of pre-B cells from Hdac3D/- bone marrow. For Hdac3D/- B cells that did show productive VDJ rearrangement, there was significant skewing toward the incorporation of proximal VH gene segments and a corresponding reduction in distal VH gene segment usage. While transcriptional effects within these loci were modest, Hdac3D/- progenitor cells displayed global changes in chromatin structure that likely hindered effective distal V-DJ recombination. Re-introduction of wild type Hdac3 restored normal B cell development, whereas an Hdac3 point mutant lacking deacetylase activity failed to complement this defect. Thus, the deacetylase activity of Hdac3 is required for the generation of mature B cells.
2017-06-05 | GSE98649 | GEO
Project description:Histone Deacetylase 3 is required for efficient T cell development
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Project description:The repertoire of diverse T-cell receptors (TCRs) and immunoglobulins is generated through restrictedly lineage and stage specific DNA rearrangements of variable (V), diversity (D) and Joining (J) gene segments at early T and B cell development. Histone modifications has been demonstrated to ensure proper VDJ recombination. However, the epigenetic mechanisms and the role of enzymes that catalyze epigenetic modifications in regulating VDJ recombination still remain largely unexplored. Herein we report that deletion of SetD2, the histone methyltransferase to catalyze the trimethylation of lysine 36 on histone 3, leads to severe lymphopenia due to development blockage of T lymphocyte at the double negative 3 (DN3) stage and differentiation arrest of B cell development at the pro-B stage in genetically engineered mouse models. SetD2 deficiency causes a loss of H3K36me3 and markedly impairs VDJ rearrangement of TCRβ and immunoglobulin heavy chain. Our study demonstrates that SetD2 and its mediated H3K36M3 modification are required for the VDJ recombination and normal lymphocyte development.
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Project description:Nuclear Receptor Corepressors are Required for the Histone Deacetylase Activity of HDAC3 In Vivo (Microarray)
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Project description:Nuclear Receptor Corepressors are Required for the Histone Deacetylase Activity of HDAC3 In Vivo (ChIP-Seq)
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Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
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Project description:Transcriptional repression by non-canonical EED stimulation of histone deacetylase activity is required for heart maturation independently of H3K27me3 [Microarray]
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