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Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers (RNA-seq data set)

ABSTRACT: Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers (RNA-seq data set)

PROVIDER: PRJNA445652 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6895270.fastq.gz	Fastqsanger.gz
	SRR6895280.fastq.gz	Fastqsanger.gz
	SRR6895290.fastq.gz	Fastqsanger.gz
	SRR6895271.fastq.gz	Fastqsanger.gz
	SRR6895291.fastq.gz	Fastqsanger.gz

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Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers

Project description:Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers

| PRJNA445646 | ENA

Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers (RNA-seq data set)

Project description:Fibroblasts can be directly reprogrammed toward a cardiac fate by introducing cardiogenic transcription factors (TFs), although the underlying mechanisms of the cardiac reprogramming process remain unclear. Three cardiac TFs, GATA4, MEF2C, and Tbx5 (referred to as GMT) can activate cardiac genes in fibroblasts and their cardiogenic activity is enhanced by the Hand2 TF and the Akt1 kinase. To understand the mechanistic basis of cardiac reprogramming, we performed a genome-wide analysis of cardiogenic TF binding sites and active enhancers, which were annotated by H3K27ac histone modification, during the reprogramming process. We found that cardiogenic TFs rapidly co-occupy core regulatory elements of cardiac genes and activate myriad cardiac enhancers that are enriched predominantly in Mef2 binding sites. Addition of Hand2 and Akt1 to the GMT reprogramming cocktail expands the spectrum of co-occupied active cardiac enhancers. As reprogramming proceeds over time, reprogramming TFs continue to activate additional cardiac enhancers, which are also enriched for Mef2 motifs, while fibroblast enhancers are silenced. This transition of the enhancer landscape strongly correlated with changes in the fibroblast and cardiac transcriptome. To test the relevance of cardiac reprogramming enhancers to the regulation of cardiogenesis in vivo, we assayed a collection of reprogramming enhancers in transgenic mouse embryos and found that they directed highly specific expression patterns in the developing heart. Our findings demonstrate that Hand2 and Akt1 enhance reprogramming by facilitating cardiac enhancer occupancy and identify Mef2 as a central effector of cardiac reprogramming, which coordinates the actions of accessory factors across a broad landscape of cardiac enhancers.

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Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers (ChIP-seq data set)

2019-04-15 | GSE112315 | GEO

Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers (ChIP-seq data set)

Project description:Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers (ChIP-seq data set)

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Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers.

Project description:The cardiogenic transcription factors (TFs) Mef2c, Gata4, and Tbx5 can directly reprogram fibroblasts to induced cardiac-like myocytes (iCLMs), presenting a potential source of cells for cardiac repair. While activity of these TFs is enhanced by Hand2 and Akt1, their genomic targets and interactions during reprogramming are not well studied. We performed genome-wide analyses of cardiogenic TF binding and enhancer profiling during cardiac reprogramming. We found that these TFs synergistically activate enhancers highlighted by Mef2c binding sites and that Hand2 and Akt1 coordinately recruit other TFs to enhancer elements. Intriguingly, these enhancer landscapes collectively resemble patterns of enhancer activation during embryonic cardiogenesis. We further constructed a cardiac reprogramming gene regulatory network and found repression of EGFR signaling pathway genes. Consistently, chemical inhibition of EGFR signaling augmented reprogramming. Thus, by defining epigenetic landscapes these findings reveal synergistic transcriptional activation across a broad landscape of cardiac enhancers and key signaling pathways that govern iCLM reprogramming.

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Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers

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

2019-04-15 | GSE112317 | GEO

Super-enhancers require enhancers and facilitators to fully activate gene expression

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Super-enhancers require enhancers and facilitators to fully activate gene expression [Tiled-C]

Project description:Super-enhancers require enhancers and facilitators to fully activate gene expression [Tiled-C]

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Super-enhancers require enhancers and facilitators to fully activate gene expression [ChIP-seq]

Project description:Super-enhancers require enhancers and facilitators to fully activate gene expression [ChIP-seq]