Human skeletal muscle differentiation time course
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE4460 | GEO | 2008/03/02
SECONDARY ACCESSION(S): PRJNA94383
REPOSITORIES: GEO
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Project description:Spatiotemporal gene expression programs are orchestrated by transcriptional enhancers which interact with target-gene promoters to regulate gene expression. The BMP antagonist Gremlin1 (Grem1) is an important node in the gene regulatory network that controls vertebrate limb development. In this study, we used a combination of open chromatin profiling (ATAC-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) in mouse and chick to identify putative cis-regulatory modules (CRMs) that regulate Grem1 in limb buds. Using CRISPR/Cas genome editing we generated different Grem1 regulatory alleles lacking either individual CRMs, combinations or entire enhancer clusters. To study potential interactions of these CRMs with the Grem1 promoter, we generated 4C-seq profiles of specific regulatory alleles. Taken together our results revealed that the spatio-temporal changes in Grem1 expression are caused by cis-regulatory alterations due to the deletions of enhancer clusters rather than global changes in chromatin architecture.
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Project description:Spatiotemporal gene expression programs are orchestrated by transcriptional enhancers which interact with target-gene promoters to regulate gene expression. The BMP antagonist Gremlin1 (Grem1) is an important node in the gene regulatory network that controls vertebrate limb development. In this study, we used a combination of open chromatin profiling (ATAC-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) in mouse and chick to identify putative cis-regulatory modules (CRMs) that regulate Grem1 in limb buds. Using CRISPR/Cas genome editing we generated different Grem1 regulatory alleles lacking either individual CRMs, combinations or entire enhancer clusters. To study potential interactions of these CRMs with the Grem1 promoter, we generated 4C-seq profiles of specific regulatory alleles. Taken together our results revealed that the spatio-temporal changes in Grem1 expression are caused by cis-regulatory alterations due to the deletions of enhancer clusters rather than global changes in chromatin architecture.
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Project description:The abstract of the manuscript titled "Identification of co-regulated genes and cis-regulatory modules in Drosophila contractile cardiomyocytes" is given below: "Understanding how sets of genes are co-regulated to generate cell diversity during metazoan development is a major challenge. This requires the identification of tightly co-expressed genes in a given developmental process, of the responsible cis-regulatory modules, and of the combination of trans-acting transcription factors. We chose the Drosophila cardiac tube to address this issue. The cardiac tube is composed of a rostral aorta and a caudal heart, with distinct morphologies and functions and its development is controlled by conserved transcription factors. Our goal was to identify heart specific expressed genes and to use a combination of genetic and bioinformatic tools to identify and characterize their heart cis-regulatory modules (CRMs). By combined candidate gene approach and microarray experiments, we found 15 different genes that are specifically co-expressed in the contractile cardiomyocytes of the heart. Potential heart-specific CRMs were retrieved from evolutionary conserved non-coding sequences that were ranked according to an integrated score based on combinations of conserved occurrences of potential binding sites for transcription factors known to be expressed in the cardiovascular system, namely Abd-A, Tin, GATA, Mef2, Hand, and T-box factors. Candidate CRMs were then tested in vivo by generating nGFP reporter construct transgenic flies, allowing the identification of three heart enhancers precisely reproducing endogenous gene expression in the heart. We identified 15 genes that are tightly co-regulated in the contractile cardiomyocytes of the heart and for three of them found the responsible enhancer through computational predictions. A computational post-analysis suggests that different combinations of heart transcription factors may regulate these enhancers and permits to further refine the in silico identification of heart-specific CRMs."
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