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Coordinated transcriptional and epigenetic mechanisms that direct development of the later differentiating second heart field (SHF) progenitors remain largely unknown. Here, we show that a novel zebrafish histone deacetylase 1 (hdac1) mutant allele cardiac really gone (crg) has a deficit of ventricular cardiomyocytes (VCs) and smooth muscle within the outflow tract (OFT) due to both cell and non-cell autonomous loss in SHF progenitor proliferation. Cyp26-deficient embryos, which have increased retinoic acid (RA) levels, have similar defects in SHF-derived OFT development. We found that nkx2.5+ progenitors from Hdac1 and Cyp26-deficient embryos have ectopic expression of ripply3, a transcriptional co-repressor of T-box transcription factors that is normally restricted to the posterior pharyngeal endoderm. Furthermore, the ripply3 expression domain is expanded anteriorly into the posterior nkx2.5+ progenitor domain in crg mutants. Importantly, excess ripply3 is sufficient to repress VC development, while genetic depletion of Ripply3 and Tbx1 in crg mutants can partially restore VC number. We find that the epigenetic signature at RA response elements (RAREs) that can associate with Hdac1 and RA receptors (RARs) becomes indicative of transcriptional activation in crg mutants. Our study highlights that transcriptional repression via the epigenetic regulator Hdac1 facilitates OFT development through directly preventing expression of the RA-responsive gene ripply3 within SHF progenitors.
Pubmed ID: 31091225 RIS Download
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This portal leads to the numerous Wasserman Lab online software tools available for use. The following are list of active Software tools available: - ConSite: Transcription factor binding site detection using phylogenetic footprinting - dbMTN: Multiple Tissue Northern Blot Comparison Tool - Gene Set Builder: A tool for collation, curation and distribution of sets of genes - The Gene Characterization Index: a bioinformatics method for scoring the extent to which a protein-encoding gene is functionally described - JASPAR: Transcription Factor Binding Profile Database - MSCAN: Algorithm that detects clusters of transcription factor binding sites in genomic sequences - NHRscan: A computational predictor of nuclear hormone receptor binding sites - oPOSSUM: Web-based analysis of over-represented transcription factor binding sites - ORCA: Transcription factor binding site detection using phylogenetic footprinting (alternative to ConSite) - OrthoSeq: Alignment of DNA sequences - PAZAR: An open-access system for the collection and dissemination of regulatory sequence annotation - Phylofoot: Tools for phylogenetic footprinting - RAVEN: Regulatory analysis of Variation in ENhancers - SAGE2Splice: A tool that uses unmapped SAGE tags to predict novel splice junctions in the genome - TFBS: Perl modules for transcription factor binding site detection and analysis - TFCat: TFCat is a catalog of mouse and human TFs based on a reliable core collection of annotations obtained by expert review of the scientific literature. - TFe: An online encyclopedic collection of well-studied transcription factor proteins in the human, mouse, and rat genomes - Ulysses: Protein Interactions Conserved Across Evolution
View all literature mentionsImaris provides range of capabilities for working with three dimensional images. Uses flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.
View all literature mentionsA commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
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View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
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