Impact of chromatin structure on PR signaling: transition from local to global analysis

Mol Cell Endocrinol. 2012 Jun 24;357(1-2):30-6. doi: 10.1016/j.mce.2011.09.006. Epub 2011 Sep 21.

Abstract

The progesterone receptor (PR) interacts with chromatin in a highly dynamic manner that requires ongoing chromatin remodeling, interaction with chaparones and activity of the proteasome. Here we discuss dynamic interaction of steroid receptor with chromatin, with special attention not only to PR but also to the glucocorticoid receptor (GR), as these receptors share many similarities regarding interaction with, and remodeling of, chromatin. Both receptors can bind nucleosomal DNA and have accordingly been described as pioneering factors. However recent genomic approaches (ChIP-seq and DHS-seq) show that a large fraction of receptor binding events occur at pre-accessible chromatin. Thus factors which generate and maintain accessible chromatin during development, and in fully differentiated tissue, contribute a major fraction of receptor tissue specificity. In addition, chromosome conformation capture techniques suggest that steroid receptors preferentially sequester within distinct nuclear hubs. We will integrate dynamic studies from single cells and genomic studies from cell populations, and discuss how genomic approaches have reshaped our current understanding of mechanisms that control steroid receptor interaction with chromatin.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chromatin / chemistry*
  • Chromatin / genetics*
  • Gene Expression Regulation
  • Humans
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism*
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism*
  • Signal Transduction*

Substances

  • Chromatin
  • Receptors, Progesterone
  • Receptors, Steroid