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Enhancer-promoter interactions in acheiropodia patient's cells

ABSTRACT: Enhancer-promoter interactions in acheiropodia patient's cells

PROVIDER: PRJNA649358 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12341917.fastq.gz	Fastqsanger.gz
	SRR12341918.fastq.gz	Fastqsanger.gz
	SRR12341919.fastq.gz	Fastqsanger.gz
	SRR12341920.fastq.gz	Fastqsanger.gz
	SRR12341921.fastq.gz	Fastqsanger.gz

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Enhancer-promoter interactions in acheiropodia patient's cells

Project description:Acheiropodia, congenital limb truncation, is associated with homozygous deletions in the LMBR1 gene around ZRS, an enhancer regulating SHH during limb development. How these deletions leads to this phenotype is unknown. Using whole-genome sequencing, we fine-mapped the acheiropodia-associated region to 12 kb and show that it does not function as an enhancer. CTCF and RAD21 ChIP-seq together with 4C-seq and DNA FISH identify three CTCF sites within the acheiropodia-deleted region that mediate the interaction between the ZRS and the SHH promoter. This interaction is substituted with other CTCF sites centromeric to the ZRS in the disease state. Mouse knockouts of the orthologous 12 kb sequence have no apparent abnormalities, showcasing the challenges in modelling CTCF alterations in animal models due to inherent motif differences between species. Our results show that alterations in CTCF motifs can lead to a Mendelian condition due to altered enhancer-promoter interactions.

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