Medical College of Wisconsin
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Temporal dynamic reorganization of 3D chromatin architecture in hormone-induced breast cancer and endocrine resistance. Nat Commun 2019 Apr 03;10(1):1522

Date

04/05/2019

Pubmed ID

30944316

Pubmed Central ID

PMC6447566

DOI

10.1038/s41467-019-09320-9

Scopus ID

2-s2.0-85063964396 (requires institutional sign-in at Scopus site)   63 Citations

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.

Author List

Zhou Y, Gerrard DL, Wang J, Li T, Yang Y, Fritz AJ, Rajendran M, Fu X, Stein G, Schiff R, Lin S, Frietze S, Jin VX

Author

Victor X. Jin PhD Professor in the Data Science Institute department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Antineoplastic Agents, Hormonal
Breast Neoplasms
Cell Nucleus
Chromatin
Drug Resistance, Neoplasm
Epigenesis, Genetic
Estradiol
Estrogen Receptor alpha
Female
Humans
MCF-7 Cells
Models, Molecular
Promoter Regions, Genetic
Protein Binding
Signal Transduction
Tamoxifen
Transcription Factors