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

Nat Commun. 2019 Apr 3;10(1):1522. doi: 10.1038/s41467-019-09320-9.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents, Hormonal / pharmacology
  • Breast Neoplasms / chemically induced
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Nucleus / metabolism
  • Chromatin / chemistry
  • Chromatin / metabolism*
  • Drug Resistance, Neoplasm
  • Epigenesis, Genetic
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / biosynthesis
  • Estrogen Receptor alpha / genetics
  • Female
  • Humans
  • MCF-7 Cells
  • Models, Molecular
  • Promoter Regions, Genetic
  • Protein Binding
  • Signal Transduction
  • Tamoxifen / pharmacology
  • Transcription Factors

Substances

  • Antineoplastic Agents, Hormonal
  • Chromatin
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Transcription Factors
  • Tamoxifen
  • Estradiol