Genome-Wide Analysis Unveils DNA Helicase RECQ1 as a Regulator of Estrogen Response Pathway in Breast Cancer Cells

Susceptibility to breast cancer is significantly increased in individuals with germ line mutations RECQ1 (also known as RECQL or RECQL1), a gene encoding DNA helicase essential for genome maintenance. We previously reported that expression predicts clinical outcomes sporadic patients stratified by estrogen receptor (ER) status. Here, we utilized an unbiased integrative genomics approach delineate cross talk between and ERα, master regulatory transcription factor cancer. found of ESR1, the directly activated RECQ1. More than 35% binding sites were cobound ERα genome-wide. Mechanistically, cooperates FOXA1, pioneer enhance chromatin accessibility at ESR1 regions activity-dependent manner. In ERα-positive cancers treated endocrine therapy, high FOXA1 coexpressing tumors associated better survival. Collectively, these results identify novel cofactor uncover unknown mechanism which regulates disease-driving ER-positive cells.