Temporal dynamic reorganization of 3D chromatin architecture in hormone-induced breast cancer and endocrine resistance.

ABSTRACT: Recent studies have demonstrated that chromatin architecture is linked to the progression of cancers. However, the roles of 3D structure and its dynamics in hormone-dependent breast cancer and endocrine resistance are largely unknown. Here we report the dynamics of 3D chromatin structure across a time course of estradiol (E2) stimulation in human estrogen receptor ? (ER?)-positive breast cancer cells. We identified subsets of temporally highly dynamic compartments predominantly associated with active open chromatin and found that these highly dynamic compartments showed higher alteration in tamoxifen-resistant breast cancer cells. Remarkably, these compartments are characterized by active chromatin states, and enhanced ER? binding but decreased transcription factor CCCTC-binding factor (CTCF) binding. We finally identified a set of ER?-bound promoter-enhancer looping genes enclosed within altered domains that are enriched with cancer invasion, aggressiveness or metabolism signaling pathways. This large-scale analysis expands our understanding of high-order temporal chromatin reorganization underlying hormone-dependent breast cancer.

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC6447566 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature