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High-resolution genome topology of human retina uncovers super enhancer-promoter interactions at tissue-specific and multifactorial disease loci [Cut&Run]

ABSTRACT: High-resolution genome topology of human retina uncovers super enhancer-promoter interactions at tissue-specific and multifactorial disease loci [Cut&Run]

PROVIDER: PRJNA836267 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19139489_1.fastq.gz	Fastqsanger.gz
	SRR19139489_2.fastq.gz	Fastqsanger.gz
	SRR19139490_1.fastq.gz	Fastqsanger.gz
	SRR19139490_2.fastq.gz	Fastqsanger.gz
	SRR19139491_1.fastq.gz	Fastqsanger.gz

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High-resolution genome topology of human retina uncovers super enhancer-promoter interactions at tissue-specific and multifactorial disease loci.

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High-resolution genome topology of human retina uncovers super enhancer-promoter interactions at tissue-specific and multifactorial disease loci [ATAC-seq]

Project description:Chromatin organization and enhancer-promoter contacts are critical for establishing unique spatiotemporal gene expression patterns in distinct cell types. Non-coding genetic variants can influence cellular phenotypes by modifying higher-order transcriptional hubs and consequently gene expression. To elucidate transcriptional regulation by non-coding genome in human retina, we mapped chromatin contacts at high resolution and integrated this data with histone marks and super-enhancers (SEs). Retinal SEs exhibited abundant local interactions and reside in topologically associated domains (TADs) with weak boundary insulation. Notably, intra-TAD positioning of SEs correlated with the biological function of their target genes in the retina. We also identified regulatory landscapes of retinopathy genes and uncovered candidate genes for risk variants associated with age-related macular degeneration and glaucoma. Our studies of high-resolution genomic architecture of the human retina provide new insights into genetic control of tissue-specific functions, suggest paradigms for missing heritability, and enable the dissection of multifactorial disease phenotypes.

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