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An in vivo repertoire of zebrafish cardiomyocyte-specific cis-regulatory elements [ChIP-Seq]

ABSTRACT: An in vivo repertoire of zebrafish cardiomyocyte-specific cis-regulatory elements [ChIP-Seq]

PROVIDER: PRJNA1057907 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27368649.fastq.gz	Fastqsanger.gz
	SRR27368650.fastq.gz	Fastqsanger.gz
	SRR27368651.fastq.gz	Fastqsanger.gz
	SRR27368652.fastq.gz	Fastqsanger.gz

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An in vivo repertoire of zebrafish cardiomyocyte-specific cis-regulatory elements

Project description:An in vivo repertoire of zebrafish cardiomyocyte-specific cis-regulatory elements

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An in vivo repertoire of zebrafish cardiomyocyte-specific cis-regulatory elements [RNA-Seq]

Project description:cis-Regulatory elements (cREs) are essential for the spatio-temporal control of gene expression during development and disease. However, cRE activity is highly dependent on cell and tissue type. The developing heart is composed of several cell-types, predominantly cardiomyocytes. Therefore, cardiomyocytes-specific modelling is required to understand the cis-regulation of the developing heart. Zebrafish are an ideal model to study heart development, as they share a number of physiological features with the human heart during development. Therefore, we present a comprehensive cardiomyocyte-specific repertoire of cREs isolated from zebrafish larvae. This data combines live transcriptomics and epigenetic profiling, providing insights into cREs and their associated genes involved in heart development. We further perform a transgenic reporter assay for the identified cREs of bmp10 and popdc2 genes, validating these genomic regions as cardiac regulatory elements. We share this comprehensive, reproducible cardiomyocyte-specific cRE resource as an interrogable web tool for understanding the epigenetic and transcriptomic mechanisms underlying heart development and emergence of congenital heart defects.

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An in vivo repertoire of zebrafish cardiomyocyte-specific cis-regulatory elements [ChIP-Seq]

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Project description:An in vivo repertoire of zebrafish cardiomyocyte-specific cis-regulatory elements [RNA-Seq]

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An in vivo repertoire of zebrafish cardiomyocyte-specific cis-regulatory elements

Project description:This SuperSeries is composed of the SubSeries listed below.

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Genome-wide identification of putative cis-regulatory elements through epigenetic profiling in zebrafish

Project description:In this study, we have applied ChIP-Seq to identify putative regulatory elements throughout the zebrafish genome. For this purpose we identified sequences within the zebrafish genome that associate with H3K4me1 and H3K4me3, which are epigenetic modifications known to be associated with active cis-regulatory elements in other species. Determination of H3K4me1- and H3K4me3-binding sites in the zebrafish genome.

2011-02-25 | E-GEOD-20600 | biostudies-arrayexpress

Latent enhancers unveiled by stimulation expand and adapt the available cis-regulatory repertoire (FAIRE-seq)

Project description:According to current models, transcription factors (TFs) activated by extracellular stimuli operate in the context of a pre-established enhancer repertoire induced and maintained by lineage-specific TFs. Here, we uncovered the existence of latent enhancers, defined as regions of the genome that in terminally differentiated cells are poorly accessible and lack the histone marks characteristic of enhancers, but readily acquire these features in response to extracellular cues. Stimulation of resting macrophages caused simultaneous binding of stimulus-activated TFs and lineage-determining TFs to these regions, enabling deposition of enhancer-specific features. Once unveiled, these enhancers did not return to a latent state even when stimulation ceased; instead, they persisted and mediated a faster and stronger response upon restimulation. We suggest that stimulus-specific expansion of the available cis-regulatory repertoire provides an epigenomic memory of the exposure to environmental agents. Formaldehyde-Assisted Isolation Of Regulatory Elements (FAIRE) followed by multiparallel sequencing was performed in untreated murine bone marrow-derived macrophages.

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Effects of cis-regulatory elements on proteome

Project description:Background Genomic variations contribute to the phenotypic diversity of individuals. A number of polymorphisms in protein-coding regions that alter drug efficacy or lead to adverse reactions have been characterized; however, noncoding regions that affect drug responses are largely overlooked, except for a limited number of well-studied enhancers. Results We conducted a quantitative assessment of cis-regulatory elements (CREs) based on transcription initiation profiling of mRNAs and noncoding RNAs, including enhancer RNAs, by using CAGE (Cap Analysis of Gene Expression). Candidate CREs identified in a hepatocellular carcinoma HepG2 cell line with stable expression of drug-responsive transcription factor pregnane X receptor (PXR) were further narrowed down by integrating data of PXR-binding sites in human primary hepatocytes and genome-wide association studies. We found more than 100-fold enrichments of the candidates to genetically associated loci with circulating levels of bilirubin and vitamin D, which implicated a link to adverse reactions of PXR ligands. We uncovered novel enhancers of UGT1A1 and TSKU through CRISPR/Cas9 knockout experiments. We identified alleles altering regulatory activities of UGT1A1 and CYP24A1enhancers by using luciferase reporter assay. Furthermore, our siRNA experiments revealed an unexpected impact of TSKU on the expression of vitamin D-metabolizing enzymes. Conclusions Our transcriptome-based assessment of CREs expanded the list of drug-inducible and PXR-mediated enhancers and super-enhancers. We identified regulatory alleles that alter drug-induced gene expressions, and discovered a novel molecular cascade associated with an adverse reaction. Our results contribute a precise understanding of the noncoding elements of the human genome underlying drug responses.

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Predictable Engineering of Signal-Dependent Cis-Regulatory Elements

Project description:Predictable Engineering of Signal-Dependent Cis-Regulatory Elements

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