Epigenetic regulation of nuclear steroid receptors Jennifer E. Leader a,b,c , Chenguang Wang a,b , Maofu Fu a,b , Richard G. Pestell a,b, * a Kimmel Cancer Center, Department of Cancer Biology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, United States b Kimmel Cancer Center, Department of Medical Oncology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, United States c Interdisciplinary Program in Tumor Biology, Georgetown University, Washington, DC 20057, United States biochemical pharmacology 72 (2006) 1589–1596 article info Article history: Received 1 May 2006 Accepted 30 May 2006 Keywords: Nuclear receptors Androgen receptor Estrogen receptor Peroxisome proliferator activated receptor Epigenetics Histone Abbreviations: NR, nuclear receptor AR, androgen receptor ERa, estrogen receptor PPARg, peroxisome proliferator- activated receptor g HAT, histone acetyltransferase HDAC, histone deacetylase SRC, steroid receptor coactivator N-CoR, nuclear receptor corepresssor SMRT, silencing mediator of retinoid and thyroid hormone receptor TSA, trichostatin A SIRT1, Sirtuin 1 CBP, CREB binding protein p/CAF, p300/CBP-associated factor DNMT, DNA methyltransferase abstract Histone modifier proteins have come to the forefront in the study of gene regulation. It is now known that histone methyltransferases, acetytransferases, kinases, ubiquitinases, deacetylases and demethylases orchestrate expression of target genes by modifying both histone and non-histone proteins. The nuclear receptor (NR) superfamily govern such diverse biological processes as development, physiology and disease, including human cancer. The involvement of NR in complexes with coactivators and corepressors is neces- sary for regulation of target genes. This review focuses on the newly recognized interactions between the NR and histone modifying enzymes. In addition to regulating histones, the histone modifying proteins directly modify and thereby regulate NR activity. In the same manner that signaling platforms exist within the histone tails that are post-translationally processed by histone modifying proteins, cascades of post-translational modification have been identified within the NR that coordinate their activity. This review focuses on the regulation of the NR estrogen receptor (ERa), androgen receptor (AR) and peroxisome proliferator activated receptor-gamma (PPARg), given their role in tumor onset and pro- gression. # 2006 Elsevier Inc. All rights reserved. * Corresponding author. Tel.: +1 215 503 5649; fax: +1 215 503 9334. E-mail addresses: Richard.Pestell@jefferson.edu, Dawn.Scardino@mail.jci.tju.edu (R.G. Pestell). available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/biochempharm 0006-2952/$ – see front matter # 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.bcp.2006.05.024