Publication
Temporal dynamic reorganization of 3D chromatin architecture in hormone-induced breast cancer and endocrine resistance.
Zhou Yufan, Gerrard Diana L, Wang Junbai, Li Tian, Yang Yini, Fritz Andrew J, Rajendran Mahitha, Fu Xiaoyong, Stein Gary, Schiff Rachel, Lin Shili, Frietze Seth, Jin Victor X
# 3D Chromatin Dynamics in Hormone-Dependent Breast Cancer
This study investigates how three-dimensional chromatin architecture dynamically reorganizes in response to estradiol stimulation in estrogen receptor α–positive (ERα+) breast cancer cells and how these changes differ in tamoxifen-resistant cells. The researchers tracked chromatin structure changes over a time course of hormone stimulation in MCF-7 breast cancer cells, identifying compartments that undergo temporal reorganization during estrogen signaling.
The analysis revealed that temporally dynamic chromatin compartments are enriched for active chromatin states and enhanced ERα binding, but show reduced binding of the architectural protein CTCF. Notably, these highly dynamic compartments are more substantially altered in tamoxifen-resistant cells compared to hormone-sensitive cells. The researchers identified genes within reorganized domains that associate with cancer invasion, aggressiveness, and metabolic signaling pathways, and many contain ERα-bound promoter-enhancer looping elements.
These findings establish a link between three-dimensional chromatin reorganization and hormone-dependent breast cancer progression and endocrine resistance, suggesting that dynamic chromatin remodeling plays a role in transcriptional reprogramming underlying therapeutic 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 α (ERα)-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 ERα binding but decreased transcription factor CCCTC-binding factor (CTCF) binding. We finally identified a set of ERα-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.