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Homo sapiens

ABSTRACT: MPRA analysis of the enhancer activity of human accelerated regions in human iPSC-derived neural cell lines

PROVIDER: PRJNA428579 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6745470_1.fastq.gz	Fastqsanger.gz
	SRR6745470_2.fastq.gz	Fastqsanger.gz
	SRR6745480_1.fastq.gz	Fastqsanger.gz
	SRR6745480_2.fastq.gz	Fastqsanger.gz
	SRR6745490_1.fastq.gz	Fastqsanger.gz

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Project description:Human accelerated regions (HARs) are evolutionarily conserved sequences that acquired human-specific nucleotide changes and reside in genomic regions associated with unique human traits and disease. The majority of HARs (96%) are noncoding, a few of which have been shown to be functional enhancers. Here, we comprehensively tested human and chimpanzee sequences of HARs (N=714) for enhancer activity using a lentivirus-based massively parallel reporter assay (lentiMPRA) in human and chimpanzee iPSC derived neural progenitors at two differentiation time points. We found that 43% (306/714) function as enhancers and over two-thirds (204/306) showed consistent differences in activity between human and chimpanzee sequences across conditions. We also tested all possible permutations of substitutions in seven HARs and found significant positive and negative interactions. Our study provides a comprehensive resource of functional neurodevelopmental HAR enhancers and shows that multiple interacting sites drive evolutionary activity differences.

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