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PROVIDER: PRJNA293413 | ENA |
REPOSITORIES: ENA
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Project description:Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis [microarray]
| PRJNA310968 | ENA
Project description:Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis [Chip-Seq]
| PRJNA310767 | ENA
Project description:Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis [RNA-Seq]
| PRJNA310768 | ENA
Project description:Dominant mutations in cardiac transcription factor genes cause human inherited congenital heart defects (CHDs), but their molecular basis is not understood. Transcription factors and Brg1/Brm-associated factor (BAF) chromatin remodeling complex interactions suggest potential mechanisms, but the role of BAF complexes in cardiogenesis is not known. Here we show that dosage of Brg1 is critical for mouse and zebrafish cardiogenesis. Disrupting the balance between Brg1 and disease-causing cardiac transcription factors, including Tbx5, Tbx20, and Nkx2-5, causes severe cardiac anomalies, revealing an essential allelic balance between Brg1 and these cardiac transcription factor genes. This suggests that relative levels of transcription factors and BAF complexes are important for heart development, which is supported by reduced occupancy of Brg1 at cardiac genes in Tbx5 haploinsufficient hearts. Our results reveal complex dosage-sensitive interdependence between transcription factors and BAF complexes, providing a potential mechanism underlying transcription factor haploinsufficiency, with implications for multigenic inheritance of CHDs. We performed transcriptional profiling of E11.5 hearts from mice heterozygous for deletions of Brg1, Tbx5, or Nkx2-5, and mice that were compound heterozygotes for Brg1 and each transcription factor gene (Tbx5 and Nkx2-5).
2010-12-22 | E-GEOD-26191 | biostudies-arrayexpress
Project description:Dominant mutations in cardiac transcription factor genes cause human inherited congenital heart defects (CHDs), but their molecular basis is not understood. Transcription factors and Brg1/Brm-associated factor (BAF) chromatin remodeling complex interactions suggest potential mechanisms, but the role of BAF complexes in cardiogenesis is not known. Here we show that dosage of Brg1 is critical for mouse and zebrafish cardiogenesis. Disrupting the balance between Brg1 and disease-causing cardiac transcription factors, including Tbx5, Tbx20, and Nkx2-5, causes severe cardiac anomalies, revealing an essential allelic balance between Brg1 and these cardiac transcription factor genes. This suggests that relative levels of transcription factors and BAF complexes are important for heart development, which is supported by reduced occupancy of Brg1 at cardiac genes in Tbx5 haploinsufficient hearts. Our results reveal complex dosage-sensitive interdependence between transcription factors and BAF complexes, providing a potential mechanism underlying transcription factor haploinsufficiency, with implications for multigenic inheritance of CHDs.
2010-12-22 | GSE26191 | GEO
Project description:Rationale: Cardiogenesis is regulated by a complex interplay between transcription factors and chromatin-modifying enzymes. However, little is known about how these interactions regulate the transition from mesodermal precursors to cardiac progenitor cells (CPCs). Objective: To identify novel regulators of mesodermal cardiac lineage commitment. Methods and Results: We performed a bioinformatic-based transcription factor-binding site analysis on upstream promoter regions of genes that are enriched in ES cell-derived CPCs. From 32 candidate transcription factors screened, we found that YY1, a repressor of sarcomeric gene expression, is present in CPCs in vivo. Interestingly, we uncovered the ability of YY1 to transcriptionally activate Nkx2.5, a key marker of early cardiogenic commitment. YY1 regulates Nkx2.5 expression via a 2.1 kb cardiac-specific enhancer as demonstrated by in vitro luciferase-based assays and in vivo chromatin immunoprecipitation (ChIP) and genome-wide sequencing analysis. Furthermore, the ability of YY1 to activate Nkx2.5 expression depends on its cooperative interaction with GATA4 at a nearby chromatin. Cardiac mesoderm-specific loss-of-function of YY1 resulted in early embryonic lethality. This was corroborated in vitro by ES cell-based assays where we show that the over-expression of YY1 enhanced the cardiogenic differentiation ES cells into CPCs in a cell autonomous manner. Conclusion: These results demonstrate an essential and unexpected role for YY1 to promote cardiogenesis as a transcriptional activator of Nkx2.5 and other CPC-enriched genes. We report the identification of putative YY1 target genes in cardiac progenitor cells (CPCs). Two samples of independently FACS-purified eGFP+ CPCs were examined against the input.
2013-06-01 | E-GEOD-35370 | biostudies-arrayexpress
Project description:Nucleosomes that contain the histone variant H2A.Z are enriched around transcriptional start sites in many organisms. A single octameric nucleosome can contain two H2A.Z histones (homotypic) or one H2A.Z and one canonical H2A (heterotype). We generated high-resolution maps of homotypic and heterotypic Drosophila H2A.Z (H2Av) nucleosomes. Although homotypic and heterotypic H2Av nucleosomes map throughout most of the genome, homotypic nucleosomes are enriched and heterotypic nucleosomes are depleted downstream of active promoters and intron/exon boundaries. The distribution of homotypic H2A.Z nucleosomes resembles that of salt-soluble nucleosomes and shows evidence of displacement during transcriptional elongation. Homotypic nucleosomes are also depleted downstream of paused polymerases, where salt-soluble nucleosomes are conspicuously depleted. Our results suggest a model whereby H2A.Z enrichment patterns result from different structural interactions within the core of heterotypic and homotypic nucleosomes following disruption during transcriptional elongation. We analyzed two replicates for input, heterotypic and homotypic purifications. We sequenced one library for each of the single H2Av pulldown and 80mM salt soluble samples.
2010-11-01 | E-GEOD-21615 | biostudies-arrayexpress
Project description:The goal of the ChIP-seq study was to investigate the distribution of the TATA-binding protein (TBP) across the human genome. TBP is the DNA-binding subunit of the basal transcription factor TFIID for RNA polymerase II (pol II) and it also participates in other complexes for the other RNA polymerase. The BTAF1 ATPase forms a stable complex with TBP and regulates its activity in pol II transcription. BTAF1 is believed to mobilize TBP from promoter and non-promoter sites. To test this hypothesis, TBP ChIP samples were prepared from human HeLa cervix carcinoma cells after knock-down of BTAF1 expression and compared to HeLa cells with a control knock-down of GAPDH. GAPDH is a cytosolic enzyme that participates in glycolysis, and its inactivation is not expected to affect the genomic distribution of TBP, and acts as negative control. ChIP samples were sequenced using SOLiD technology along with the INPUT sample to normalize the distribution of background signals within each of the two chromatin samples. 2 ChIP samples + one input sample
2010-03-02 | E-GEOD-17937 | biostudies-arrayexpress
Project description:Functional crosstalk between histone modifications and chromatin remodeling has emerged as a key regulatory mode of transcriptional control during cell fate decisions, but the underlying mechanisms are not fully understood. Here we demonstrate that NSD2/SRC-3 complex coordinates histone H3 lysine 36 dimethylation (H3K36me2) and transcriptional elongation factor Pol II to regulate chromatin dynamic and gene transcription during myeloma resistant to bortezomib. Mechanistically, NSD2 can interact with SRC-3, its SET domain is responsible to H3K36me2 to enhance the transcriptional activity of SRC-3 target gene. The inhibitor of SRC-3, SI-2, can impaired the interaction between NSD2 and SRC-3, caused the distribution of H3K36me2 on the genome-wide.
2020-08-26 | GSE156870 | GEO
Project description:Tissue-specific transcription factors initiate differentiation toward a specialized cell type by inducing transcription-permissive chromatin modifications at target gene promoters, through the recruitment of the SWI/SNF chromatin-remodeling complex (1, 2). The molecular mechanism that regulates the chromatin re-distribution of SWI/SNF in response to differentiation signals is currently unknown. Here we show that the muscle determination factor MyoD and the SWI/SNF structural sub-unit, BAF60c (SMARCD3), form a complex on the regulatory elements of MyoD-target genes in undifferentiated myoblasts, prior to the activation of gene expression. MyoD-BAF60c complex is devoid of the ATP-dependent enzymatic sub-units Brg1 and Brm, is required for stable MyoD binding to Ebox sequences, and marks the chromatin for signal-dependent recruitment of the SWI/SNF core complex to muscle loci. BAF60c phosphorylation on a conserved threonine by differentiation-activated p38 signalling promotes the incorporation of MyoD-BAF60c into a Brg1-based SWI/SNF complex, which is competent to remodel the chromatin and activates transcription of MyoD-target genes. Our data support an unprecedented two-step model, by which pre-assembled BAF60c-MyoD complex directs the SWI/SNF complex chromatin re-distribution to muscle loci in response to differentiation cues. Differentiation of C2C12 cells individually interfered for BRG1, BAF60B, BAF60C
2011-03-07 | E-GEOD-24573 | biostudies-arrayexpress