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Consticted migration is associated with stable 3D genome structure differences in cancer cells (Hi-C)

ABSTRACT: Consticted migration is associated with stable 3D genome structure differences in cancer cells (Hi-C)

PROVIDER: PRJNA601219 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10894100_1.fastq.gz	Fastqsanger.gz
	SRR10894100_2.fastq.gz	Fastqsanger.gz
	SRR10894101_1.fastq.gz	Fastqsanger.gz
	SRR10894101_2.fastq.gz	Fastqsanger.gz
	SRR10894090_1.fastq.gz	Fastqsanger.gz

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Consticted migration is associated with stable 3D genome structure differences in cancer cells (Hi-C)

Project description:We investigated the effect of constricted migration (using transwell assays with 5-μm or 12-μm in diameter) on the organization of the 3D genome in melanoma and breast cancer cells.

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Consticted migration is associated with stable 3D genome structure differences in cancer cells (RNA-Seq)

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Consticted migration is associated with stable 3D genome structure differences in cancer cells (ATAC-Seq)

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Consticted migration is associated with stable 3D genome structure differences in cancer cells (ATAC-Seq)

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Consticted migration is associated with stable 3D genome structure differences in cancer cells (RNA-Seq)

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3D Chromosome Structure Can Reveal Stem Cell Signatures (Hi-C)

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Consticted migration is associated with stable 3D genome structure differences in cancer cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-06-29 | GSE143678 | GEO

RNA surveillance controls 3D genome structure via stable cohesin chromosome interaction

Project description:The 3D architecture that the genome is folded into is regulated by CTCF, which determines domain borders, and cohesin, which generates interactions within domains. However, organisms lacking CTCF have been reported to still have cohesin-mediated 3D structures with strong borders. How this can be achieved and precisely regulated are yet unknown. Using in situ Hi-C, we found that 3’-end RNA processing factors coupled with proper transcription termination are a cis-acting determinant that regulates the localization and dynamics of cohesin on the chromosome arms. Loss of RNA processing factors, including nuclear exosome and Pfs2, destabilizes cohesin from the 3'-ends of convergent genes and results in decreased cohesin-mediated domain boundaries. We observed the co-localization between Rad21 and a wide range of 3'end RNA processing/termination factors. Further, deletion of Rrp6 leads to cohesin redistribution to facultative heterochromatin, resulting in improper domain boundaries. Importantly, we observed that knockdown of Rrp6Exosc10 caused a defect in cohesin binding and loss of local topologically associating domains (TADs) interactions in mouse embryonic stem cells. Based on these findings, we propose a novel function of the RNA surveillance pathway in 3D genome organization via cohesin complex, which provides the molecular basis underlying the dynamics of cohesin function.

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Constricted migration is associated with stable 3D genome structure differences in cancer cells

Project description:To spread from a localized tumor, metastatic cancer cells squeeze through constrictions that cause major nuclear deformations. Since chromosome structure affects nucleus stiffness, gene regulation and DNA repair, here we investigate the relationship between 3D genome structure and constricted migration in cancer cells. Using melanoma (A375) cells, we identify phenotypic differences in cells that have undergone multiple rounds of constricted migration. These cells display a stably higher migration efficiency, elongated morphology, and differences in the distribution of Lamin A/C and heterochromatin. Hi-C experiments reveal differences in chromosome spatial compartmentalization specific to cells that have passed through constrictions and related alterations in expression of genes associated with migration and metastasis. Certain 3D genome structure changes, such as a loss of B compartment interaction strength, are consistently observed after constricted migration in clonal populations of A375 cells and in MDA-MB-231 breast cancer cells. Our observations suggest that consistent types of chromosome structure changes are induced or selected by passage through constrictions and that these may epigenetically encode stable differences in gene expression and cellular migration phenotype.

| S-SCDT-EMBOR-2020-52149-T | biostudies-other

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