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Serial Inversions Induce Tissue-specific Architectural Stripes, Gene Misexpression and Congenital Malformations [cHi-C]

ABSTRACT: Serial Inversions Induce Tissue-specific Architectural Stripes, Gene Misexpression and Congenital Malformations [cHi-C]

PROVIDER: PRJNA480257 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7500320_1.fastq.gz	Fastqsanger.gz
	SRR7500320_2.fastq.gz	Fastqsanger.gz
	SRR7500321_1.fastq.gz	Fastqsanger.gz
	SRR7500321_2.fastq.gz	Fastqsanger.gz
	SRR7500315_1.fastq.gz	Fastqsanger.gz

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Serial Inversions Induce Tissue-specific Architectural Stripes, Gene Misexpression and Congenital Malformations [cHi-C]

Project description:Here we study the effect of balanced chromosomal rearrangements (BCRs) on gene expression in vivo in mouse embryos by generating a series of genomic inversions that place an active enhancer cluster located in the Epha4 regulatory domain at different positions within a neighboring gene dense region. Expression studies in embryonic limb buds show that the inverted enhancer cluster was able to activate several genes downstream of its new position, resulting in gene misexpression and limb phenotypes. Capture Hi-C from mutant limb buds showed that the activated genes were located within a region of asymmetric three-dimensional contacts, so called architectural stripes. Deletion of the CTCF binding site at that position of the stripe anchor resulted in a collapse of the stripes, down regulation of ectopic gene expression, and a rescue of the skeletal phenotype. In cells in which the enhancers are not active, such as mouse embryonic stem cells (mESCs), stripes do not form, indicating that their formation is also dependent on enhancer activity. Based on HiC from limb buds we show that architectural stripes are a frequent feature in the genome often associated with developmentally active enhancers. Thus, BCRs can induce ectopic gene expression via the formation of asymmetric chromatin contacts. The formation of these stripes is dependent on CTCF anchors and enhancer activity.

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