Expression data of mouse developmental T cells (CD4CD8DP, CD4SP and CD8SP) derived from Brd1 deficient thymocyte
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE48797 | GEO | 2014/05/24
SECONDARY ACCESSION(S): PRJNA211803
REPOSITORIES: GEO
Similar Datasets
Project description:Conditional knock out of Brd1(bromodomain containing 1) in muse developmental T cells (CD4CD8DP, CD4SP and CD8SP) by intercrossing with Tie2-Cre Conditional knock out of Brd1(bromodomain containing 1) in muse MHC class l restricted T cells (CD8SP) by intercrossing with Tie2-Cre and OT-l Developmental T cells (defined by surface markers: CD4, CD8 and TCR?) derived from control (Tie2-Cre) or Brd1 conditional knock out (Brd1flox/flox, Tie2-Cre) thymocytes were isolated by fluorescence activated cell sorting (FACS) and subjected to a microarray analysis. CD8SP T cells were also isolated from control (Tie2-Cre, OT-l) or Brd1 conditional knock out (Brd1flox/flox, Tie2-Cre, OT-l) thymocytes intercrossed with OT-l.
2014-05-24 | E-GEOD-48797 | biostudies-arrayexpress
Project description:The BRCA1 tumor suppressor has many functions in DNA damage repair, DNA replication, and beyond. Loss of any of these functions can lead to breast and ovarian carcinogenesis and also therapeutic sensitivity. In this study, we have discovered a novel role for BRCA1 in controlling replication initiation by regulating the bromodomain-protein BRD1 and the histone acetyltransferase HBO1. Specifically, we show that BRCA1 regulates localization of the BRD1-HBO1 complex to replication origins where the complex normally acetylates histone H3 on lysine 14. We performed chromatin-immunoprecipitation seqeuncing (ChIP-seq) for BRD1 and HBO1 in a BRCA1 mutant line (UWB1.289) and demonstrate that BRD1 and HBO1 co-occupy ORC2 binding sites and replication origins.
2024-01-11 | GSE244027 | GEO
Project description:Switch defective/sucrose non-fermentable chromatin remodeling complexes are multi-subunit machines that play vital roles in regulating chromatin structure and gene expression. However, how SWI/SNF complexes recognize target loci is still not fully understood. Here, we show that Arabidopsis bromodomain-containing homologous proteins, BRD1, BRD2 and BRD13, are core subunits of SWI/SNF complexes that are required for SWI/SNF genomic targeting. The three BRDs directly interact with multiple SWI/SNF subunits, including the BRAHMA (BRM) catalytic subunit. Phenotypic and transcriptome analysis of the brd1 brd2 brd13 triple mutants showed that the BRDs act in large redundancy to control developmental processes and gene expression that are also regulated by BRM. BRDs extensively co-localize with BRM on chromatin. brd1 brd2 brd13 mutation results in the reduced BRM protein levels and genome-wide targeting on chromatin. Finally, we demonstrate that the bromodomain of BRD2 is essential for genomic targeting of BRD2, highlighting the role of this reader domain in the recruitment of BRM-containing SWI/SNF complexes to target sites in plants. SWI/SNF chromatin remodeling complexes are evolutionarily conserved and is confirmed to use the energy derived from hydrolysis of ATP to alter the density or the position of nucleosomes on the DNA or the composition of histone octamer. Bromodomain, an acetylated histone interaction module, was found in chromatin remodeling factors. During the 29 Arabidopsis bromodomain-containing protein, like GCN5 and GTE4/6, their function has been reported. Here, we reported three BRM-interacting bromodomain-containing protein, BRD1, BRD2 and BRD13 are new core subunits of Arabidopsis SWI/SNF complexes. brd1/2/13 displayed a similar phenotype like brm, such as down-ward curled leaves, reduced fertility, shorter silique and root. Moreover, brm brd1/2/13 shows more serious phenotype just like brm-1. Y2H, Co-IP, RNA-seq and ChIP-seq assay reveal that BRDs interact with BRM at both protein and chromatin level. Future more, BRDs are required for BRM genome-wide occupancy and BRM might bind to chromatin via BRDs bromodomain by interacting with their BBC domain.
2021-03-22 | GSE161515 | GEO
Project description:Background: The bromodomain containing 1 (BRD1) gene has been implicated with transcriptional regulation, brain development and susceptibility to schizophrenia and bipolar disorder. Results: To advance the understanding of BRD1 and its role in mental disorders, we characterized the protein and chromatin interactions of the BRD1 isoforms, BRD1-S and BRD1-L, by a series of investigations and integration of functional molecular data with human genetic data. We present several novel protein interactions of BRD1, including proteins previously implicated with mental disorders. By BRD1-S and BRD1-L chromatin immunoprecipitation followed by next generation sequencing we identified binding to promoter regions of 1540 and 823 genes, respectively, and showed correlation between BRD1-S and BRD1-L binding and regulation of gene expression. The identified BRD1 interaction network was found to be predominantly co-expressed with BRD1 mRNA in human brain and enriched for pathways involved in gene expression and brain function. By interrogation of large data sets from genome-wide association studies, we further demonstrate that the BRD1 interaction network is enriched for schizophrenia risk. Conclusion: Our results show that BRD1 interacts with chromatin remodeling proteins, e.g. PBRM1, as well as histone modifiers, e.g. MYST2 and SUV420H1. We find that BRD1 primarily binds in close proximity to transcription start sites and regulates expression of numerous genes, many of which are involved with brain development and susceptibility to mental disorders. Our findings indicate that BRD1 acts as a regulatory hub in a comprehensive schizophrenia risk network which plays a role in many brain regions throughout life, implicating e.g.striatum, hippocampus, and amygdala at mid fetal stages. 9 expression arrays performed in HEK293T cells
2016-03-16 | E-GEOD-79255 | biostudies-arrayexpress
Project description:Background: The bromodomain containing 1 (BRD1) gene has been implicated with transcriptional regulation, brain development and susceptibility to schizophrenia and bipolar disorder. Results: To advance the understanding of BRD1 and its role in mental disorders, we characterized the protein and chromatin interactions of the BRD1 isoforms, BRD1-S and BRD1-L, by a series of investigations and integration of functional molecular data with human genetic data. We present several novel protein interactions of BRD1, including proteins previously implicated with mental disorders. By BRD1-S and BRD1-L chromatin immunoprecipitation followed by next generation sequencing we identified binding to promoter regions of 1540 and 823 genes, respectively, and showed correlation between BRD1-S and BRD1-L binding and regulation of gene expression. The identified BRD1 interaction network was found to be predominantly co-expressed with BRD1 mRNA in human brain and enriched for pathways involved in gene expression and brain function. By interrogation of large data sets from genome-wide association studies, we further demonstrate that the BRD1 interaction network is enriched for schizophrenia risk. Conclusion: Our results show that BRD1 interacts with chromatin remodeling proteins, e.g. PBRM1, as well as histone modifiers, e.g. MYST2 and SUV420H1. We find that BRD1 primarily binds in close proximity to transcription start sites and regulates expression of numerous genes, many of which are involved with brain development and susceptibility to mental disorders. Our findings indicate that BRD1 acts as a regulatory hub in a comprehensive schizophrenia risk network which plays a role in many brain regions throughout life, implicating e.g.striatum, hippocampus, and amygdala at mid fetal stages.
2016-03-16 | GSE79255 | GEO
Project description:Genetic and molecular studies have implicated the bromodomain containing 1 (BRD1) gene in the pathogenesis of schizophrenia and bipolar disorder. Accordingly, mice heterozygous for a targeted deletion of Brd1 (Brd1+/- mice) show behavioural phenotypes with broad translational relevance to psychiatric disorders. BRD1 encodes a scaffold protein that affects the expression of many genes through modulation of histone acetylation. BRD1 target genes have been identified in cell lines; however the impact of reduced Brd1 levels on the brain proteome is largely unknown. In this study, we applied label-based quantitative mass spectrometry to profile the frontal cortex, hippocampus and striatum proteome and synaptosomal proteome of female Brd1+/- mice. We successfully quantified between 1537 and 2196 proteins and show widespread changes in protein abundancies. By integrative analysis of human genetic data, we find that the differentially abundant proteins in frontal cortex are enriched for schizophrenia risk further linking the actions of BRD1 to psychiatric disorders. Affected proteins were further enriched for proteins involved in processes known to influence neuronal and dendritic spine morphology e.g. regulation of actin cytoskeleton dynamics and mitochondrial function. Directly prompted in these findings, we investigated dendritic spine morphology of pyramidal neurons in anterior cingulate cortex and found them significantly altered, including reduced size of small dendritic spines and decreased number of the mature mushroom type. Collectively, our study describes known as well as new mechanisms related to BRD1 dysfunction and its role in psychiatric disorders, and provides evidence for the molecular and cellular dysfunctions underlying altered neurosignalling and cognition in Brd1+/- mice.
2019-01-07 | PXD009691 | Pride
Project description:Genetic and molecular studies have implicated the bromodomain containing 1 (BRD1) gene in the pathogenesis of schizophrenia and bipolar disorder. Accordingly, mice heterozygous for a targeted deletion of Brd1 (Brd1+/- mice) show behavioural phenotypes with broad translational relevance to psychiatric disorders. BRD1 encodes a scaffold protein that affects the expression of many genes through modulation of histone acetylation. BRD1 target genes have been identified in cell lines; however the impact of reduced Brd1 levels on the brain proteome is largely unknown. In this study, we applied label-based quantitative mass spectrometry to profile the frontal cortex, hippocampus and striatum proteome and synaptosomal proteome of female Brd1+/- mice. We successfully quantified between 1537 and 2196 proteins and show widespread changes in protein abundancies. By integrative analysis of human genetic data, we find that the differentially abundant proteins in frontal cortex are enriched for schizophrenia risk further linking the actions of BRD1 to psychiatric disorders. Affected proteins were further enriched for proteins involved in processes known to influence neuronal and dendritic spine morphology e.g. regulation of actin cytoskeleton dynamics and mitochondrial function. Directly prompted in these findings, we investigated dendritic spine morphology of pyramidal neurons in anterior cingulate cortex and found them significantly altered, including reduced size of small dendritic spines and decreased number of the mature mushroom type. Collectively, our study describes known as well as new mechanisms related to BRD1 dysfunction and its role in psychiatric disorders, and provides evidence for the molecular and cellular dysfunctions underlying altered neurosignalling and cognition in Brd1+/- mice.
2019-01-07 | PXD009692 | Pride
Project description:Genetic and molecular studies have implicated the bromodomain containing 1 (BRD1) gene in the pathogenesis of schizophrenia and bipolar disorder. Accordingly, mice heterozygous for a targeted deletion of Brd1 (Brd1+/- mice) show behavioural phenotypes with broad translational relevance to psychiatric disorders. BRD1 encodes a scaffold protein that affects the expression of many genes through modulation of histone acetylation. BRD1 target genes have been identified in cell lines; however the impact of reduced Brd1 levels on the brain proteome is largely unknown. In this study, we applied label-based quantitative mass spectrometry to profile the frontal cortex, hippocampus and striatum proteome and synaptosomal proteome of female Brd1+/- mice. We successfully quantified between 1537 and 2196 proteins and show widespread changes in protein abundancies. By integrative analysis of human genetic data, we find that the differentially abundant proteins in frontal cortex are enriched for schizophrenia risk further linking the actions of BRD1 to psychiatric disorders. Affected proteins were further enriched for proteins involved in processes known to influence neuronal and dendritic spine morphology e.g. regulation of actin cytoskeleton dynamics and mitochondrial function. Directly prompted in these findings, we investigated dendritic spine morphology of pyramidal neurons in anterior cingulate cortex and found them significantly altered, including reduced size of small dendritic spines and decreased number of the mature mushroom type. Collectively, our study describes known as well as new mechanisms related to BRD1 dysfunction and its role in psychiatric disorders, and provides evidence for the molecular and cellular dysfunctions underlying altered neurosignalling and cognition in Brd1+/- mice.
2019-01-07 | PXD009689 | Pride
Project description:Genetic and molecular studies have implicated the bromodomain containing 1 (BRD1) gene in the pathogenesis of schizophrenia and bipolar disorder. Accordingly, mice heterozygous for a targeted deletion of Brd1 (Brd1+/- mice) show behavioural phenotypes with broad translational relevance to psychiatric disorders. BRD1 encodes a scaffold protein that affects the expression of many genes through modulation of histone acetylation. BRD1 target genes have been identified in cell lines; however the impact of reduced Brd1 levels on the brain proteome is largely unknown. In this study, we applied label-based quantitative mass spectrometry to profile the frontal cortex, hippocampus and striatum proteome and synaptosomal proteome of female Brd1+/- mice. We successfully quantified between 1537 and 2196 proteins and show widespread changes in protein abundancies. By integrative analysis of human genetic data, we find that the differentially abundant proteins in frontal cortex are enriched for schizophrenia risk further linking the actions of BRD1 to psychiatric disorders. Affected proteins were further enriched for proteins involved in processes known to influence neuronal and dendritic spine morphology e.g. regulation of actin cytoskeleton dynamics and mitochondrial function. Directly prompted in these findings, we investigated dendritic spine morphology of pyramidal neurons in anterior cingulate cortex and found them significantly altered, including reduced size of small dendritic spines and decreased number of the mature mushroom type. Collectively, our study describes known as well as new mechanisms related to BRD1 dysfunction and its role in psychiatric disorders, and provides evidence for the molecular and cellular dysfunctions underlying altered neurosignalling and cognition in Brd1+/- mice.
2019-01-07 | PXD009961 | Pride
Project description:Genetic and molecular studies have implicated the bromodomain containing 1 (BRD1) gene in the pathogenesis of schizophrenia and bipolar disorder. Accordingly, mice heterozygous for a targeted deletion of Brd1 (Brd1+/- mice) show behavioural phenotypes with broad translational relevance to psychiatric disorders. BRD1 encodes a scaffold protein that affects the expression of many genes through modulation of histone acetylation. BRD1 target genes have been identified in cell lines; however the impact of reduced Brd1 levels on the brain proteome is largely unknown. In this study, we applied label-based quantitative mass spectrometry to profile the frontal cortex, hippocampus and striatum proteome and synaptosomal proteome of female Brd1+/- mice. We successfully quantified between 1537 and 2196 proteins and show widespread changes in protein abundancies. By integrative analysis of human genetic data, we find that the differentially abundant proteins in frontal cortex are enriched for schizophrenia risk further linking the actions of BRD1 to psychiatric disorders. Affected proteins were further enriched for proteins involved in processes known to influence neuronal and dendritic spine morphology e.g. regulation of actin cytoskeleton dynamics and mitochondrial function. Directly prompted in these findings, we investigated dendritic spine morphology of pyramidal neurons in anterior cingulate cortex and found them significantly altered, including reduced size of small dendritic spines and decreased number of the mature mushroom type. Collectively, our study describes known as well as new mechanisms related to BRD1 dysfunction and its role in psychiatric disorders, and provides evidence for the molecular and cellular dysfunctions underlying altered neurosignalling and cognition in Brd1+/- mice.
2019-01-07 | PXD009690 | Pride