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Topological isolation as a mechanism for precise control of developmental regulators in mammalian genomes

ABSTRACT: Topological isolation as a mechanism for precise control of developmental regulators in mammalian genomes

PROVIDER: PRJNA524324 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13509159_1.fastq.gz	Fastqsanger.gz
	SRR13509159_2.fastq.gz	Fastqsanger.gz
	SRR13509160_1.fastq.gz	Fastqsanger.gz
	SRR13509160_2.fastq.gz	Fastqsanger.gz
	SRR13509161_1.fastq.gz	Fastqsanger.gz

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Topological isolation as a mechanism for precise control of developmental regulators in mammalian genomes [HiC]

Project description:Developmental regulators are spatiotemporal regulated in the process of human development. Recent investigation of insulated chromosome structures suggests their crucial role in control of proper gene expression. However, it’s unclear whether developmental regulators can be precisely controlled by such insulated structures and whether developmental failure can be caused by disrupting the structure boundaries. Here we identified topologically insulated regions (TIRs) from deeply sequenced human embryonic stem cell (hESC) Hi-C data and analyzed the gene distribution across TIRs. We found a notable enrichment of developmental regulators isolated from other genes by TIRs and show that the boundary CTCF sites are highly conserved across species. Perturbation of such boundaries in hESCs leads to the differentiation failure. Germline mutations affecting such boundaries are subject to purifying selection, and are underrepresented in the human population. Further analyses demonstrated the enhancer activity is restricted by such boundaries that further points towards regulatory importance. Our findings provide new insights into mammalian genome organization and including a possible role of gene insulation through chromosomal folding structures for precise control of developmental regulators.

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Topological isolation as a mechanism for precise control of developmental regulators in mammalian genomes [RNA-seq]

Project description:Recent investigation of insulated chromosome structures suggests their crucial role in controlling proper gene expression. However, it remains unclear whether developmental regulators can be precisely controlled by such insulated structures and whether developmental failure is caused by disrupting the structure boundaries. Here we identified topologically insulated regions (TIRs) from deeply sequenced human embryonic stem cell (hESC) Hi-C data and analyzed the gene distribution across TIRs. We find a notable enrichment of developmental regulators isolated from other genes by TIRs and show that the boundary CTCF sites are highly conserved across species. Perturbation of such boundaries in hESCs leads to failure to properly differentiate. Enhancer activity is restricted by such boundaries, further pointing towards their regulatory importance. Finally, germline mutations affecting such boundaries are subject to purifying selection and are underrepresented in the human population. Our findings provide new insights into mammalian genome organization and suggest a possible role of gene insulation through chromosomal folding structures for precise control of developmental regulators.

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