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An atlas of transcribed human cardiac promoters and enhancers reveals an important role of regulatory elements in heart failure

ABSTRACT: An atlas of transcribed human cardiac promoters and enhancers reveals an important role of regulatory elements in heart failure

PROVIDER: PRJNA633482 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16506300.fastq.gz	Fastqsanger.gz
	SRR16506400.fastq.gz	Fastqsanger.gz
	SRR16506301.fastq.gz	Fastqsanger.gz
	SRR16506302.fastq.gz	Fastqsanger.gz
	SRR16506303.fastq.gz	Fastqsanger.gz

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An atlas of transcribed human cardiac promoters and enhancers reveals an important role of regulatory elements in heart failure

Project description:In this work we present atlas of human cardiac regulatory elements defined by CAGE (cap analysis of gene expression) technique. The dataset includes right and left atria and ventricles form both healthy and failing samples. The deep sequencing of CAGE libraries on Illumina HiSeq2500, mapping, and signal clustering resulted in identification of 65,458 CAGE peaks, from which 55,204 were robust decomposition peak identifiers (DPIs) and 10,254 bidirectional enhancers. We created comprehensive classification of the peaks by applying machine learning along with annotation from available databases containing cardiac data. Identified CAGE peaks were arranged into non-overlapping 400 bp consensus clusters. Our classification method determined 17,668 promoters and 14,920 enhancers active in the human heart. Differential expression analysis revealed regulatory elements activated or inactivated in healthy or failing states. About 10% of heart related GWAS SNPs were found to be located around heart CAGE clusters. The library of cardiac promoters and enhancers is available in Zenbu reports for browsing and visualization. Superior and inferior sinoatrial node samples are labeled as sSAN and iSAN, respectively.

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Project description:Recent works have shown that RNA Polymerase (Pol) II can be recruited to, and transcribe, distal regulatory regions. Here, we analyzed transcription initiation and elongation through genome-wide localization of Pol II, General Transcription Factors (GTFs) and active chromatin in developing T-cells. We show that Pol II and GTFs are recruited to known, highly T-cell-specific enhancers. We extend this observation for the first time to many new putative enhancers, a majority of which are transcribed with or without polyadenylation. Importantly, we also identify genomic features characterized by large Pol II/GTFs recruitment and Transcriptional Initiation Platforms (TIPs) at promoters, intergenic and intragenic regions. TIPs are characterized by variable widths (0.4 to 10 kb), and correlate with high CpG content and tissue-specificity at promoters. Finally, we also report differential recruitment of TFIID and other GTFs at promoters and enhancers. Overall, we propose that TIPs represent important novel regulatory hallmarks of the genome. This study is based on the analysis of 20 samples in mouse double-positive thymocytes, 15 of which cover a range of general and specific transcription factors, chromatin modifying enzymes as well as histone modifications. 2 samples were dedicated for strand-specific RNA sequencing either from the total RNA population or after a selection of Poly(A) RNA. A Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) sample has been sequenced in order to isolate open chromatin regions. Finally, input and IG control samples were designed and sequenced for data processing purposes. Biological and technical replicates were processed as described in the supplementary methods.

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