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A reference map of cardiac transcription factor chromatin occupancy identifies dynamic and conserved transcriptional enhancers

ABSTRACT: A reference map of cardiac transcription factor chromatin occupancy identifies dynamic and conserved transcriptional enhancers

PROVIDER: PRJNA510592 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11798798.fastq.gz	Fastqsanger.gz
	SRR8335330.fastq.gz	Fastqsanger.gz
	SRR8335340.fastq.gz	Fastqsanger.gz
	SRR8335350.fastq.gz	Fastqsanger.gz
	SRR8335331.fastq.gz	Fastqsanger.gz

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A reference map of cardiac transcription factor chromatin occupancy identifies dynamic and conserved transcriptional enhancers

Project description:Mapping the chromatin occupancy of transcription factors (TFs) is a key step in deciphering the transcriptional programs that orchestrate organ development and homeostasis. Here we used biotinylated knockin alleles of seven key TFs (GATA4, NKX2-5, MEF2A, MEF2C, SRF, TBX5, TEAD1) that regulate heart development and homeostasis to sensitively and reproducibly map their genome-wide occupancy in the fetal and adult heart. Our results show that these TFs have dynamic chromatin occupancy between developmental stages. We observed that multiple TFs often co-occupy the same chromatin region, exhibiting collaborative binding that overall was most consistent with indirect cooperativity. Regions with multiple TF binding were more likely to exhibit features of functional regulatory elements, including evolutionary conservation, chromatin accessibility, and activity in transcriptional enhancer assays. Although histone H3 acetylation on lysine 27 (H3K27ac) has been used to identify active enhancers, many regions occupied by multiple TFs lacked H3K27ac, and TF-bound regions with or without H3K27ac co-occupancy had similar region conservation and enhancer activity. Specific studies of TEAD1 demonstrated that it is a core component of the cardiac transcriptional network: physically interacted with NKX2-5 and MEF2C and co-occupied regulatory loci with other cardiac TFs to regulate cardiomyocyte-specific gene functions. Our study shows that co-occupancy by multiple TFs is a hallmark of a subset of functional transcriptional regulatory elements and provides a rich resource for deciphering the cardiac transcriptional regulatory network.

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A reference map of murine cardiac transcription factor chromatin occupancy identifies dynamic and conserved enhancers.

Project description:Mapping the chromatin occupancy of transcription factors (TFs) is a key step in deciphering developmental transcriptional programs. Here we use biotinylated knockin alleles of seven key cardiac TFs (GATA4, NKX2-5, MEF2A, MEF2C, SRF, TBX5, TEAD1) to sensitively and reproducibly map their genome-wide occupancy in the fetal and adult mouse heart. These maps show that TF occupancy is dynamic between developmental stages and that multiple TFs often collaboratively occupy the same chromatin region through indirect cooperativity. Multi-TF regions exhibit features of functional regulatory elements, including evolutionary conservation, chromatin accessibility, and activity in transcriptional enhancer assays. H3K27ac, a feature of many enhancers, incompletely overlaps multi-TF regions, and multi-TF regions lacking H3K27ac retain conservation and enhancer activity. TEAD1 is a core component of the cardiac transcriptional network, co-occupying cardiac regulatory regions and controlling cardiomyocyte-specific gene functions. Our study provides a resource for deciphering the cardiac transcriptional regulatory network and gaining insights into the molecular mechanisms governing heart development.

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