Differential DNase I hypersensitivity reveals factor-dependent chromatin dynamics

Genome Res. 2012 Jun;22(6):1015-25. doi: 10.1101/gr.133280.111. Epub 2012 Apr 16.

Abstract

Transcription factor cistromes are highly cell-type specific. Chromatin accessibility, histone modifications, and nucleosome occupancy have all been found to play a role in defining these binding locations. Here, we show that hormone-induced DNase I hypersensitivity changes (ΔDHS) are highly predictive of androgen receptor (AR) and estrogen receptor 1 (ESR1) binding in prostate cancer and breast cancer cells, respectively. While chromatin structure prior to receptor binding and nucleosome occupancy after binding are strikingly different for ESR1 and AR, ΔDHS is highly predictive for both. AR binding is associated with changes in both local nucleosome occupancy and DNase I hypersensitivity. In contrast, while global ESR1 binding is unrelated to changes in nucleosome occupancy, DNase I hypersensitivity dynamics are also predictive of the ESR1 cistrome. These findings suggest that AR and ESR1 have distinct modes of interaction with chromatin and that DNase I hypersensitivity dynamics provides a general approach for predicting cell-type specific cistromes.

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

  • Binding Sites
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Chromatin / metabolism*
  • Deoxyribonuclease I / metabolism*
  • Estrogen Receptor alpha / metabolism*
  • Estrogens / metabolism
  • Estrogens / pharmacology
  • Female
  • Hepatocyte Nuclear Factor 3-alpha / metabolism
  • Humans
  • Male
  • Nuclear Receptor Coactivator 3 / metabolism
  • Nucleosomes / metabolism
  • Predictive Value of Tests
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Receptors, Androgen / metabolism*
  • Transcription Factors / metabolism

Substances

  • AR protein, human
  • Chromatin
  • Estrogen Receptor alpha
  • Estrogens
  • FOXA1 protein, human
  • Hepatocyte Nuclear Factor 3-alpha
  • Nucleosomes
  • Receptors, Androgen
  • Transcription Factors
  • estrogen receptor alpha, human
  • NCOA3 protein, human
  • Nuclear Receptor Coactivator 3
  • Deoxyribonuclease I

Associated data

  • GEO/GSE33216