Expression Data comparing Gene Expression in 27-day old testes of wild-type and Brwd1-/- mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE56482 | GEO | 2014/07/04
SECONDARY ACCESSION(S): PRJNA243419
REPOSITORIES: GEO
Shared Molecules
Only show the datasets with similarity scores above: 0.5
Threshold
0.5
Similar Datasets
Project description:The Brwd1 mutation, though having dramatic effects on the spermatocyte transcriptome, had little effect on the oocyte transcriptome. Postmeiotic gene expression is essential for development and maturation of sperm and eggs. In B6/C3H females, Brwd1 ablation causes severe chromosome condensation and structural defects associated with abnormal telomere structure. In contrast to males, transcriptome analysis at the germinal vesicle stage revealed only minor changes in gene expression including a >2 fold overexpression of the histone methyltransferase MLL5 and LINE-1 elements transposons. Thus, loss of BRWD1 function interferes with the completion of oogenesis and spermatogenesis through sexually dimorphic mechanisms. Our results demonstrate that BRWD1 is essential for the epigenetic control of chromosome stability during female meiosis while playing a critical role in haploid gene transcription during the post-meiotic differentiation events of spermiogenesis.
2014-12-31 | GSE56724 | GEO
Project description:Transcription factor (TF) networks determine cell fate in hematopoiesis. However, how TFs cooperate with other regulatory mechanisms to instruct transcription remains poorly understood. We demonstrate in small pre-B cells, that the lineage restricted epigenetic reader BRWD1 closes early development enhancers and opens the enhancers of late B lymphopoiesis to TF binding. BRWD1 differentially regulated over 7000 genes including repressing proliferative and inducing differentiation programs. However, BRWD1 did not regulate expression of transcription factors required for B lymphopoiesis. Hypogammaglobulinemia patients with BRWD1 mutations had B cell transcriptional profiles and enhancer landscapes similar to those observed in Brwd1-/- mice. These data indicate that in both mice and humans, BRWD1 is a master orchestrator of enhancer accessibility that cooperates with TF networks to drive late B cell development.
2018-08-11 | GSE103057 | GEO
Project description:Trisomy 21 [Down syndrome/DS] is the most common genetic cause of intellectual disability worldwide. Despite much progress in the genetic characterization of DS, the genes encoded from chromosome 21 (HSA21) that directly contribute to intellectual disability remain incompletely understood. Here, we found that a largely uncharacterized chromatin effector protein, BRWD1, is triplicated in DS neurons and brain of trisomic mice. We demonstrated that selective copy number restoration of Brwd1 in DS animals rescues transcriptional, synaptic and cognitive deficits. We showed that Brwd1 binds to the neuronal BAF chromatin remodeling complex, and that such interactions promote BAF’s genomic mistargeting in DS-like brain. Brwd1 renormalization in trisomic animals rescues these aberrant chromatin events. These findings thus establish BRWD1 as a critical epigenomic mediator of DS related phenotypes.
2022-09-22 | GSE151255 | GEO
Project description:B lymphopoiesis requires that immunoglobulin genes be accessible to RAG1-RAG2 recombinase. However, the RAG proteins bind widely to open chromatin, which suggests that additional mechanisms must restrict RAG-mediated DNA cleavage. Here we show that developmental downregulation of interleukin 7 (IL-7)-receptor signaling in small pre-B cells induced expression of the bromodomain-family member BRWD1, which was recruited to a specific epigenetic landscape at Igk dictated by pre–BCR-dependent Erk activation. BRWD1 enhanced RAG recruitment, increased gene accessibility and positioned nucleosomes 5? to each J? recombination signal sequence. BRWD1 thus targets recombination to Igk and places recombination within the context of signaling cascades that control B cell development. Our findings represent a paradigm in which,at any particular antigen-receptor locus, specialized mechanisms enforce lineage- and stage-specific recombination. ChIP-seq for 1 transcription factor and 2 histone modifications in flow purified mouse small pre-B cells. ATAC-seq and RNA-seq in WT and Brwd-Mut mouse flow purified small pre-B cells.
2015-08-24 | E-GEOD-63302 | biostudies-arrayexpress
Project description:With an astounding incidence of ~1 in 800 births, Down syndrome (DS) is the most common chromosomal condition linked to intellectual disability worldwide. While the genetic basis of DS has been identified as a triplication of chromosome 21 (HSA21), the genes encoded from HSA21 that directly contribute to cognitive deficits remain incompletely understood. Here, we found that the HSA21-encoded chromatin effector, BRWD1, was upregulated in Down syndrome neurons and brain of trisomic mice. We showed that selective copy number restoration of Brwd1 in trisomic animals rescued deficits in hippocampal LTP, cognition and gene expression. We demonstrated that Brwd1 tightly binds the BAF chromatin remodeling complex, and that increased Brwd1 expression promotes BAF genomic mistargeting. Importantly, Brwd1 renormalization rescued aberrant BAF localization, along with associated changes in chromatin accessibility and gene expression. These findings establish BRWD1 as a key epigenomic mediator of normal neurodevelopment and an important contributor to DS-related phenotypes.
2022-09-21 | GSE210117 | GEO
Project description:DICER has a well-characterized role in the processing of microRNAs (miRNAs) and small interfering RNAs (siRNA) that are important for post-transcriptional gene regulation. Emerging evidence suggests that DICER also has several non-canonical functions beyond miRNA/siRNA biogenesis, for example in transcriptional gene silencing at the chromatin level, as well as in RNA degradation and maintenance of genomic integrity. We have shown that the function of DICER in germ cells is essential for normal spermatogenesis; male mice lacking DICER in postnatal male germ cells are infertile due to severe defects in haploid differentiation. To better understand the function of DICER in male germ cells, we immunoprecipitated DICER from juvenile mouse testes and performed mass spectrometric analysis to identify DICER-interacting proteins.
2020-06-03 | PXD017772 | Pride
Project description:Lymphocyte development consists of sequential and mutually exclusive cell states of proliferative selection and antigen receptor gene recombination. Transitions between each state require large, coordinated changes in epigenetic landscapes and transcriptional programs. How this occurs remains unclear. Herein, we demonstrate that in small pre-B cells, the lineage and stage-specific epigenetic reader BRWD1 reorders three-dimensional chromatin topology to affect transition between proliferative and gene recombination molecular programs. BRWD1 regulated the switch between poised and active enhancers interacting with promoters and coordinated this with Igk locus contraction. BRWD1 did so by converting chromatin-bound static cohesin to dynamic complexes competent to mediate long-range looping. Remarkably, ATP depletion recapitulated cohesin distributions observed in Brwd1-/- cells. Therefore, in small pre-B cells, cohesin conversion appears to be the main energetic mechanism dictating where dynamic looping occurs in the genome. Our findings provide a new mechanism of cohesin regulation and reveal how cohesin function can be regulated by lineage contextual mechanisms to facilitate specific cell fate transitions.
2023-08-31 | GSE221518 | GEO
Project description:Lymphocyte development consists of sequential and mutually exclusive cell states of proliferative selection and antigen receptor gene recombination. Transitions between each state require large, coordinated changes in epigenetic landscapes and transcriptional programs. How this occurs remains unclear. Herein, we demonstrate that in small pre-B cells, the lineage and stage-specific epigenetic reader BRWD1 reorders three-dimensional chromatin topology to affect transition between proliferative and gene recombination molecular programs. BRWD1 regulated the switch between poised and active enhancers interacting with promoters and coordinated this with Igk locus contraction. BRWD1 did so by converting chromatin-bound static cohesin to dynamic complexes competent to mediate long-range looping. Remarkably, ATP depletion recapitulated cohesin distributions observed in Brwd1-/- cells. Therefore, in small pre-B cells, cohesin conversion appears to be the main energetic mechanism dictating where dynamic looping occurs in the genome. Our findings provide a new mechanism of cohesin regulation and reveal how cohesin function can be regulated by lineage contextual mechanisms to facilitate specific cell fate transitions.
2023-08-31 | GSE221517 | GEO
Project description:B lymphopoiesis requires that immunoglobulin genes be accessible to RAG1-RAG2 recombinase. However, the RAG proteins bind widely to open chromatin, which suggests that additional mechanisms must restrict RAG-mediated DNA cleavage. Here we show that developmental downregulation of interleukin 7 (IL-7)-receptor signaling in small pre-B cells induced expression of the bromodomain-family member BRWD1, which was recruited to a specific epigenetic landscape at Igk dictated by pre–BCR-dependent Erk activation. BRWD1 enhanced RAG recruitment, increased gene accessibility and positioned nucleosomes 5′ to each Jκ recombination signal sequence. BRWD1 thus targets recombination to Igk and places recombination within the context of signaling cascades that control B cell development. Our findings represent a paradigm in which,at any particular antigen-receptor locus, specialized mechanisms enforce lineage- and stage-specific recombination.
2015-08-24 | GSE63302 | GEO
Project description:Gene expression is tightly linked to histone acetylation on lysine residues that can be recognized by bromodomains. The testis-specific bromodomain protein tBRD-1 is essential for male fertility and might act as a co-factor of testis-specifc TAFs. Here, we perform microarray analyses and demonstrate that tBRD-1 selectively controls gene expression in male germ cells
2014-08-08 | GSE52511 | GEO