Abstract 2960: Factor dependent chromatin structure and nucleosome dynamics

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 (≥DHS) are highly predictive of androgen receptor (AR) and estrogen receptor (ER) binding in prostate cancer and breast cancer cells, respectively. The chromatin structure prior to binding and the nucleosome occupancy after binding are strikingly different for ER and AR. AR binding is associated with changes in both the local nucleosome occupancy and the DNase I hypersensitivity. In contrast, while globally ER binding is unrelated to changes in nucleosome occupancy, DNase I hypersensitivity dynamics predict the ER cistrome. These findings suggest that AR and ER have distinct modes of interaction with chromatin and that DNase I hypersensitivity dynamics provides a general approach for predicting cell-type specific cistromes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2960. doi:1538-7445.AM2012-2960