3-D chromatin conformation, accessibility, and gene expression profiling of triple-negative breast cancer

Author:

Llinàs-Arias Pere,Ensenyat-Méndez Miquel,Orozco Javier I. J.,Íñiguez-Muñoz Sandra,Valdez Betsy,Wang Chuan,Mezger Anja,Choi Eunkyoung,Tran Yan Zhou,Yao Liqun,Bonath Franziska,Olsen Remi-André,Ormestad Mattias,Esteller Manel,Lupien Mathieu,Marzese Diego M.

Abstract

Abstract Objectives Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype with limited treatment options. Unlike other breast cancer subtypes, the scarcity of specific therapies and greater frequencies of distant metastases contribute to its aggressiveness. We aimed to find epigenetic changes that aid in the understanding of the dissemination process of these cancers. Data description Using CRISPR/Cas9, our experimental approach led us to identify and disrupt an insulator element, IE8, whose activity seemed relevant for cell invasion. The experiments were performed in two well-established TNBC cellular models, the MDA-MB-231 and the MDA-MB-436. To gain insights into the underlying molecular mechanisms of TNBC invasion ability, we generated and characterized high-resolution chromatin interaction (Hi-C) and chromatin accessibility (ATAC-seq) maps in both cell models and complemented these datasets with gene expression profiling (RNA-seq) in MDA-MB-231, the cell line that showed more significant changes in chromatin accessibility. Altogether, our data provide a comprehensive resource for understanding the spatial organization of the genome in TNBC cells, which may contribute to accelerating the discovery of TNBC-specific alterations triggering advances for this devastating disease.

Funder

Instituto de Salud Carlos III

Balearic Islands Health Research Institute

Govern de les Illes Balears, Spain

Asociación Española Contra el Cancer

EASI-Genomics 3rd Call

Publisher

Springer Science and Business Media LLC

Subject

Health Informatics,Genetics

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