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Mus musculus
4 Downloadable Samples
Illumina HiSeq 2500
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. Overall design: Bone marrow was isolated from Hdac3+/+Mb1cre+/- or Hdac3F/-Mb1cre+/- mice at 8 weeks of age. B220+CD43+ B cells were isolated from marrow by FACS and cells from two mice were pooled per sample. Total RNA isolated by Trizol extraction.
Publication Title
Deacetylase activity of histone deacetylase 3 is required for productive <i>VDJ</i> recombination and B-cell development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples
GSE73535- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Histone Deacetylase 3 Is Required for Efficient T Cell Development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Hdac3 is an important target of HDAC inhibitors used in the treatment of cutaneous T cell lymphoma. In order to gain an understanding of Hdac3 function in T cells,we deleted Hdac3 from early mouse thymocytes using LCK-Cre. Hdac3 deletion resulted in a loss of single positive thymocytes due to a defect in positive selection at the double positive (DP) stage of thymocyte development. To better characterize this defect, we sorted the DP1 and DP2 populations to for gene expression profiling. Overall design: Total RNA was extracted from DP1 (GFP+CD4+CD8+CD5loTCRblo) or DP2 (GFP+CD4+CD8+CD5hiTCRbint) thymocytes isolated by FACS from Hdac3+/+ or Hdac3F/F LCK-Cre+ animals. Libraries were constructed from rRNA-depleted total RNA pools to identify altered gene expression in DP populations following Hdac3 deletion.
Publication Title
Histone Deacetylase 3 Is Required for Efficient T Cell Development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Treg dysfunction is associated with a variety of inflammatory diseases. Treg populations are defined by expression of the oligomeric transcription factor FOXP3 and inability to produce IL-2, a cytokine required for T cell maintenance and survival. FOXP3 activity is regulated post-translationally by histone/protein acetyltransferases and histone/protein deacetylases (HDACs). Here, we determined that HDAC3 mediates both the development and function of the two main Treg subsets, thymus-derived Tregs and induced Tregs (iTregs). We determined that HDAC3 and FOXP3 physically interact and that HDAC3 expression markedly reduces Il2 promoter activity. In murine models, conditional deletion of Hdac3 during thymic Treg development restored Treg production of IL-2 and blocked the suppressive function of Tregs. HDAC3-deficient mice died from autoimmunity by 4-6 weeks of age; however, injection of WT FOXP3+ Tregs prolonged survival. Adoptive transfer of Hdac3-deficient Tregs, unlike WT Tregs, did not control T cell proliferation in naive mice and did not prevent allograft rejection or colitis. HDAC3 also regulated the development of iTregs, as HDAC3-deficient conventional T cells were not converted into iTregs under polarizing conditions and produced large amounts of IL-2, IL-6, and IL-17. We conclude that HDAC3 is essential for the normal development and suppressive functions of thymic and peripheral FOXP3+ Tregs.
Publication Title
FOXP3+ regulatory T cell development and function require histone/protein deacetylase 3.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
In this study we demonstrate that Tgif1 has a role in HSCs maintenance, self-renewal and quiescence. RNA sequencing data of LSK cells (HSCs enriched cell population) from Tgif1-/- and wild type mice implicates that multiple pathways involved in HSC quiescence and self-renewal are disturbed in Tgif1 deficient mice. Overall design: RNA expression profiles of wild type (WT) and Tgif1-/- LSK cells were generated by RNA sequencing, in triplicate, using Illumina HiSeq 2000.
Publication Title
Tgif1 regulates quiescence and self-renewal of hematopoietic stem cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Requirement for the histone deacetylase Hdac3 for the inflammatory gene expression program in macrophages.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Pan-Hdac inhibitors (HDACi) are endowed with a potent anti-inflammatory activity, but the relative role of each of the eleven Hdac proteins sensitive to HDACi to the inflammatory gene expression program is unknown. Using an integrated genomic approach we found that Hdac3-deficient macrophages are unable to activate almost half of the inflammatory gene expression program when stimulated with lipopolysaccharide (LPS). A large part of the activation defect is due to loss of basal and LPS-inducible expression of IFNb, which in basal cells maintains Stat1 protein levels, and after stimulation acts in an autocrine/paracrine manner to promote a secondary wave of Stat1-dependent gene expression. We show that loss of Hdac3-mediated repression of nuclear receptors leads to hyperacetylation of thousands of genomic sites and associated gene derepression. The upregulation of the constitutively expressed prostaglandin endoperoxide synthase, Ptgs1 (Cox-1), has a causative role in the phenotype, since its chemical inhibition reverts the Ifnb activation defect. These data may have relevance for the use of selective Hdac inhibitors as anti-inflammatory agents.
Publication Title
Requirement for the histone deacetylase Hdac3 for the inflammatory gene expression program in macrophages.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
B220+GL7+ (GC) and B220+GL7- (non-GC) B cells were sorted from SRBC-immunized mice deficient for Hdac3 and wild type controls. RNA-sequencing revealed an upregulation of critical regulators of B cell differentiation in Hdac3-deleted animals. Overall design: 10 days post-immunization with SRBCs, GC and non-GC B cells were sorted and RNA isolated by Trizol extraction for RNA-sequencing. 2 replicates were sequenced for each condition.
Publication Title
Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus, Homo sapiens
- 2 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
ETO family protein Mtg16 regulates the balance of dendritic cell subsets by repressing Id2.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
E protein transcription factors specify major immune cell lineages including lymphocytes and interferon-producing plasmacytoid dendritic cells (pDCs). Corepressors of the ETO family can bind to and block transactivation by E proteins, but the physiological role of these interactions remained unclear. We report that ETO protein Mtg16 binds chromatin primarily through the pDC-specific E protein E2-2 in human pDCs. Mtg16-deficient mice showed impaired pDC development and functionality, whereas the specification of the classical dendritic cells (cDCs) was enhanced. The deletion of Mtg16 caused aberrant expression of E protein antagonist Id2 in pDCs. Thus, Mtg16 acts as a cofactor of E2-2 to promote pDC differentiation and restrict cDC development, revealing an unexpected positive role of ETO proteins in E protein activity.
Publication Title
ETO family protein Mtg16 regulates the balance of dendritic cell subsets by repressing Id2.
Sample Metadata Fields
Specimen part
View Samples