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

Yufan Zhou, Diana L. Gerrard, Junbai Wang, Tian Li, Yini Yang, Andrew J. Fritz, Mahitha Rajendran, Xiaoyong Fu, Rachel Schiff, Shili Lin, Seth Frietze, Victor X. Jin

Research output: Contribution to journalArticle

5 Scopus 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.

Original languageEnglish (US)
Article number1522
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Zhou, Y., Gerrard, D. L., Wang, J., Li, T., Yang, Y., Fritz, A. J., Rajendran, M., Fu, X., Schiff, R., Lin, S., Frietze, S., & Jin, V. X. (2019). Temporal dynamic reorganization of 3D chromatin architecture in hormone-induced breast cancer and endocrine resistance. Nature communications, 10(1), [1522]. https://doi.org/10.1038/s41467-019-09320-9