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Complexity of the RAR‐Mediated Transcriptional Regulatory Programs

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The Biochemistry of Retinoic Acid Receptors I: Structure, Activation, and Function at the Molecular Level

Part of the book series: Subcellular Biochemistry ((SCBI,volume 70))

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?

Z. Liu and Q. Hu made equal contributions.

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Abbreviations

3′UTR:

3′ untranslated region

AF1:

Active function 1 domain

AF2:

Active function 2 domain

AP1:

Activating protein 1

AR:

Androgen receptor

atRA:

All-trans retinoic acid

ChIP:

Chromatin immunoprecipitation

CSB:

Cockayne syndrome B protein

CTCF:

CCCTC-binding factor

DBD:

DNA binding domain

DCP1A:

mRNA-decapping enzyme 1A

DCP2:

mRNA-decapping enzyme 2

DR:

Direct repeat

ER:

Estrogen receptor

ER:

Everted repeat

ERCC1:

Excision repair cross-complementing protein 1

eRNA:

Enhancer RNA

ESCs:

Embryonic stem cells

GR:

Glucocorticoid receptor

HMGCS2:

3-Hydroxy-3-Methylglutaryl-Coenzyme A Synthase 2

HRE:

Hormone response element

IR:

Inverted repeat

LBD:

Ligand-binding domain

LC‐ESI‐MS:

Liquid chromatography-electrospray ionization–mass spectrometry

lncRNA:

Long non-coding RNA

MAPK:

Mitogen-activated protein kinase‎

NCoR:

Nuclear receptor corepressor

ncRNA:

Non‐coding RNA

NER:

Nucleotide excision repair

NR:

Nuclear receptor

PKA:

Protein kinase A

Pol II:

RNA polymerase II

Pol III:

RNA polymerase III

PPAR:

Peroxisome proliferator-activated receptor

RA:

Retinoic acid

RAR:

Retinoic acid receptor

RARE:

Retinoic acid response element

RPA:

Replication protein A

RXR:

Retinoid X receptor

SRA:

Steroid receptor RNA activator

STAT3:

Signal transducer and activator of transcription 3

TBL1:

Transducin-beta-like protein 1

TBLR1:

Transducin beta-like 1-related protein 1

TF3C:

General transcription factor 3C

TF IIF:

Transcription factor IIF

TR:

Thyroid hormone receptor

XPA:

Xeroderma pigmentosum, complementation group A

XPC:

Xeroderma pigmentosum, complementation group C

XPF:

Xeroderma pigmentosum, complementation group F

XPG:

Xeroderma pigmentosum, complementation group G

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Acknowledgments

We thank members in the Rosenfeld laboratory for suggestions and comments on this manuscript, and the editing efforts of Rachel Pardee. M.G.R. is an investigator with HHMI.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Department of Medicine, University of California, La Jolla, San Diego, CA, USA

    Zhijie Liu, Qidong Hu & Michael G. Rosenfeld

  2. Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Qidong Hu

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  1. Zhijie Liu
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  2. Qidong Hu
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  3. Michael G. Rosenfeld
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Correspondence to Zhijie Liu or Michael G. Rosenfeld .

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Editors and Affiliations

  1. Department of Biological Sciences, Tennessee State University, Nashville, Tennessee, USA

    Mary Ann Asson-Batres

  2. IGBMC, Illkirch Cedex, France

    Cécile Rochette-Egly

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Liu, Z., Hu, Q., Rosenfeld, M.G. (2014). Complexity of the RAR‐Mediated Transcriptional Regulatory Programs. In: Asson-Batres, M., Rochette-Egly, C. (eds) The Biochemistry of Retinoic Acid Receptors I: Structure, Activation, and Function at the Molecular Level. Subcellular Biochemistry, vol 70. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9050-5_10

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