Using Enhancer Activity Profiles to Explore Transcriptional Perturbations in Breast Cancer

CAMILA D. ARCUSCHIN; DENISE MUÑOZ; IGNACIO E. SCHOR

Paraná, Entre Ríos

Congreso; LIV Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2019

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

The identity and function of a cell are determined by gene regulatory networks, the de-regulation of which can lead to pathologies such as cancer. Enhancers are key genetic elements in these networks and the alteration of their function can lead to de-regulation of genes involved in oncogenic and/or tumor suppressor pathways. Furthermore, it is known that there are highly active regulatory regions, or super-enhancers (SE), with important participation in tumorigenic processes. The objective of this project is to find new relevant cellular pathways in different breast tumor types. For this, we analyzed the enhancer activity and transcriptional profiles in 17 breast cancer cell lines. First, we used ChIP-seq data for the H3K27ac histone modification to call peaks in each line, which were then combined into a unified set of regulatory regions. By merging nearby enhancers and ranking them according to their signal strength, we similarly defined a common SE set. Subsequently, we quantified the H3K27ac signal for each line across the common set of regulatory regions. We grouped the lines according to their histological subtype, and obtained differentially active regions for each group, from where we extracted the enriched motifs and their corresponding transcription factors. In parallel, using RNA-seq data in the context of breast cancer gene regulatory networks, we identified the master regulators that are differentially active in each group. The integration of these approaches would point to regulatory pathways super- and sub-active in the different breast cancer types, opening the possibilities for new lines of research.