Complexity of the RAR‐mediated transcriptional regulatory programs

Zhijie Liu, Qidong Hu, Michael G. Rosenfeld

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

In the past several decades, intensive research in this field has uncovered a surprising number of regulatory factors and their associated enzymatic properties to reveal the network of complexes that function in activation and repression of the transcriptional programs mediated by nuclear receptors (NR). These factors and their associated complexes have been extensively characterized both biochemically and functionally [34, 87, 94]. Several principles have emerged: (1) It is widely recognized that ligand-dependent cofactor complexes mediating repression and activation exhibit ligand-dependent exchange. (2) These complexes mediate modifications of chromatin structure consequent to their binding at regulatory elements, particularly at promoter and enhancer sites. (3) The concept about the rapid exchange of coregulatory complexes at regulatory sites has been suggested [88]. Key questions in the NR field have included: (a) What are the cofactors and exchange complexes used to mediate the ligand and signaling network-dependent switches in gene regulation programs; (b) Do long non-coding RNAs (lncRNAs) serve as regulatory “factors” for ligand-dependent gene programs, and do enhancers actually regulate transcription units encoding enhancer non-coding RNAs (eRNAs) that might have functional significance; (c) What is the relationship between DNA damage repair machinery and transcriptional machinery? (d) Do Retinoic Acid Receptors (RAR) also regulate Pol III-dependent, non-coding repeat transcriptional units in stem cells? and (e) How have new technologies such as deep sequencing altered our ability to investigate transcriptional regulatory mechanisms utilized by NRs?

Original languageEnglish (US)
Pages (from-to)203-225
Number of pages23
JournalSub-Cellular Biochemistry
Volume70
DOIs
StatePublished - May 29 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology
  • Cancer Research

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