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The deacetylase activity of histone deacetylase 3 is required for productive VDJ recombination and B cell development [ATAC-seq]

ABSTRACT: The deacetylase activity of histone deacetylase 3 is required for productive VDJ recombination and B cell development [ATAC-seq]

PROVIDER: PRJNA385894 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5515770_1.fastq.gz	Fastqsanger.gz
	SRR5515770_2.fastq.gz	Fastqsanger.gz
	SRR5515771_1.fastq.gz	Fastqsanger.gz
	SRR5515771_2.fastq.gz	Fastqsanger.gz
	SRR5515768_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

The deacetylase activity of histone deacetylase 3 is required for productive VDJ recombination and B cell development [RNA-seq]

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

The deacetylase activity of histone deacetylase 3 is required for productive VDJ recombination and B cell development [ATAC-seq]

2017-06-05 | GSE98649 | GEO

The deacetylase activity of histone deacetylase 3 is required for productive VDJ recombination and B cell development

Project description:The deacetylase activity of histone deacetylase 3 is required for productive VDJ recombination and B cell development

| PRJNA385811 | ENA

Deacetylase activity of histone deacetylase 3 is required for productive VDJ recombination and B-cell development.

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 Ig 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 Hdac3?/- bone marrow. For Hdac3?/- 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 use. Although transcriptional effects within these loci were modest, Hdac3?/- progenitor cells displayed global changes in chromatin structure that likely hindered effective distal V-DJ recombination. Reintroduction 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.

| S-EPMC5559004 | biostudies-literature

The deacetylase activity of histone deacetylase 3 is required for productive VDJ recombination and B cell development

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-06-05 | GSE98651 | GEO

Unbiased quantification of immunoglobulin diversity at the DNA level with VDJ-seq

Project description:For high-throughput sequencing and quantification of immunoglobulin repertoires, most methodologies utilise RNA. However, output varies enormously between recombined genes due to different promoter strengths and differential activation of lymphocyte subsets, precluding quantitation of recombinants on a per cell basis. To date, DNA-based approaches have used V gene primer cocktails, with substantial inherent biases. Here we describe VDJ-seq, which accurately quantitates immunoglobulin diversity at the DNA level in an unbiased manner. This is accomplished with a single primer extension step using biotinylated J gene primers. By addition of unique molecular identifiers (UMI) before primer extension, we reliably remove duplicate sequences and correct for sequencing and PCR errors. Furthermore, VDJ-seq captures productive and non-productive VDJ and DJ recombination events on a per cell basis. Library preparation takes 3 days, with 2 days of sequencing, and 1 day of data processing and analysis.

2017-12-16 | GSE106458 | GEO

Mus musculus

Project description:The deacetylase activity of histone deacetylase 3 is required for productive VDJ recombination and B cell development [RNA-seq]

| PRJNA385893 | ENA

SHLD1 is dispensable for 53BP1-dependent V(D)J recombination but critical for productive class switch recombination

Project description:The shieldin (SHLD) complex, composed of SHLD1, SHLD2, SHLD3 and MAD2L2/REV7, acts downstream of 53BP1 to counteract DNA double-strand break (DSB) end-resection and promote non-homologous end-joining (NHEJ). While 53BP1 is essential for immunoglobulin heavy chain class switch recombination (CSR), long-range V(D)J recombination and for repair of RAG-induced DSBs in XLF-deficient cells, the role of SHLD in these activities remains elusive. Here, we report that contrary to 53BP1, SHLD1 is dispensable for lymphocyte development and V(D)J recombination, even in the sensitized XLF-deficient background or for the joining of distant V(D)J segments. By contrast, SHLD1 restricts resection at AID-induced DSB ends in both NHEJ-proficient and NHEJ-deficient B cells, providing an end-protection mechanism that permits productive CSR. Finally, we show that this end-protection function is required for orientation-specific joining of AID-initiated DSBs. We propose that 53BP1 promotes V(D)J recombination and CSR through two distinct mechanisms; the synapsis of V(D)J segments and switch regions within chromatin independently of SHLD and the protection of AID-DSB ends against resection mediated by SHLD.

2022-05-11 | GSE202567 | GEO

SHLD1 is dispensable for 53BP1-dependent V(D)J recombination but critical for productive class switch recombination

Project description:SHLD1 is dispensable for 53BP1-dependent V(D)J recombination but critical for productive class switch recombination

| PRJNA836576 | ENA

Nuclear Receptor Corepressors are Required for the Histone Deacetylase Activity of HDAC3 In Vivo

Project description:Histone deacetylase 3 (HDAC3) is an epigenome-modifying enzyme that is required for normal mouse development and tissue-specific functions. In vitro, HDAC3 protein itself has minimal enzyme activity, but gains its histone deacetylation function from stable association with the conserved deacetylase activation domain (DAD) contained in nuclear receptor corepressors NCOR1 and SMRT. Here we show that HDAC3 enzyme activity is undetectable in mice bearing point mutations in the DAD of both NCOR1 and SMRT (NS-DADm), despite normal levels of HDAC3 protein. Local histone acetylation is increased, and genomic HDAC3 recruitment is reduced though not abrogated. Remarkably, the NS-DADm mice are born and live to adulthood, whereas genetic deletion of HDAC3 is embryonic lethal. These findings demonstrate that nuclear receptor corepressors are required for HDAC3 enzyme activity in vivo, and suggest that a deacetylase-independent function of HDAC3 may be required for life. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series.

2013-01-01 | E-GEOD-42541 | biostudies-arrayexpress

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