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An enhancer cluster controls gene activity and topology of the SCN5A-SCN10A locus in vivo (Hi-C)

ABSTRACT: An enhancer cluster controls gene activity and topology of the SCN5A-SCN10A locus in vivo (Hi-C)

PROVIDER: PRJNA529888 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8815730.fastq.gz	Fastqsanger.gz
	SRR8815721.fastq.gz	Fastqsanger.gz
	SRR8815731.fastq.gz	Fastqsanger.gz
	SRR8815722.fastq.gz	Fastqsanger.gz
	SRR8815732.fastq.gz	Fastqsanger.gz

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An enhancer cluster controls gene activity and topology of the SCN5A-SCN10A locus in vivo (Hi-C)

Project description:High-resolution chromosome conformation capture-sequencing of RE6-9 heterozygous mutants. We investigated the three-dimensional organization of the Scn5a-Scn10a locus in whole hearts of RE6-9 heterozyous mutants and wildtype littermates. Viewpoint were set on enhancer 1 (enh1, located in the intronic region of Scn10a) and the Scn5a promoter (P1_2). The liver of FVB mice was used as controle tissue to determine the specificity of the Scn5a-Scn10a interaction domain in the heart.

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An enhancer cluster controls gene activity and topology of the SCN5A-SCN10A locus in vivo

Project description:An enhancer cluster controls gene activity and topology of the SCN5A-SCN10A locus in vivo

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An enhancer cluster controls gene activity and topology of the SCN5A-SCN10A locus in vivo (RNA-Seq)

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An enhancer cluster controls gene activity and topology of the SCN5A-SCN10A locus in vivo.

Project description:Mutations and variations in and around SCN5A, encoding the major cardiac sodium channel, influence impulse conduction and are associated with a broad spectrum of arrhythmia disorders. Here, we identify an evolutionary conserved regulatory cluster with super enhancer characteristics downstream of SCN5A, which drives localized cardiac expression and contains conduction velocity-associated variants. We use genome editing to create a series of deletions in the mouse genome and show that the enhancer cluster controls the conformation of a >0.5 Mb genomic region harboring multiple interacting gene promoters and enhancers. We find that this cluster and its individual components are selectively required for cardiac Scn5a expression, normal cardiac conduction and normal embryonic development. Our studies reveal physiological roles of an enhancer cluster in the SCN5A-SCN10A locus, show that it controls the chromatin architecture of the locus and Scn5a expression, and suggest that genetic variants affecting its activity may influence cardiac function.

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An enhancer cluster controls gene activity and topology of the SCN5A-SCN10A locus in vivo

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An enhancer cluster controls gene activity and topology of the SCN5A-SCN10A locus in vivo (RNA-Seq)

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