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

233 Pages·2014·7.88 MB·English

by  Mary Ann Asson-Batres

Subcellular Biochemistry 70
Mary Ann Asson-Batres
Cécile Rochette-Egly E ditors
The Biochemistry
of Retinoic Acid
Receptors I: Structure,
Activation, and Function
at the Molecular Level
Subcellular Biochemistry
Volume 70
Series editor
Robin Harris, Northumberland, UK
For further volumes:
http://www.springer.com/series/6515
Mary Ann Asson-Batres · Cécile Rochette-Egly
Editors
The Biochemistry
of Retinoic Acid Receptors I:
Structure, Activation, and
Function at the Molecular
Level
1 3
Editors
Mary Ann Asson-Batres Cécile Rochette-Egly
Department of Biological Sciences IGBMC
Tennessee State University Illkirch Cedex
Nashville, TN France
USA
ISSN 0306-0225
ISBN 978-94-017-9049-9 ISBN 978-94-017-9050-5 (eBook)
DOI 10.1007/978-94-017-9050-5
Springer Dordrecht Heidelberg New York London
Library of Congress Control Number: 2014942450
© Springer Science+Business Media Dordrecht 2014
This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part
of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations,
recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or
information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar
methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts
in connection with reviews or scholarly analysis or material supplied specifically for the purpose of
being entered and executed on a computer system, for exclusive use by the purchaser of the work.
Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright
Law of the Publisher’s location, in its current version, and permission for use must always be obtained
from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance
Center. Violations are liable to prosecution under the respective Copyright Law.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
does not imply, even in the absence of a specific statement, that such names are exempt from the relevant
protective laws and regulations and therefore free for general use.
While the advice and information in this book are believed to be true and accurate at the date of
publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for
any errors or omissions that may be made. The publisher makes no warranty, express or implied, with
respect to the material contained herein.
Printed on acid-free paper
Springer is part of Springer Science+Business Media (www.springer.com)
Foreword
The nutritional importance of liposoluble compounds, such as vitamin A, for good
health has been known for a long time, but vitamin A itself, was only discovered
100 years ago. Since that time, vitamin A has been the focus of many scientific
investigations aimed at understanding its mechanism of action. A number of
epidemiologic studies performed with vitamin A-deficient populations of the
Third World and with vitamin A-deficient animals have indicated that vitamin A
is essential for vision, reproduction, growth, and development. The overall conclu-
sion was that vitamin A maintains good health from birth to death by controlling
the development and well-being of all tissues in a time and concentration depend-
ent manner.
Early research in the field focused on vision, and in the 1940s, it was estab-
lished that a metabolite of vitamin A, 11-cis-retinaldehyde, is the visual chromo-
phore. However, the mechanism of action of vitamin A in the regulation of cell
proliferation and differentiation throughout life was not uncovered until 1987,
when nuclear receptors for retinoic acid, another active derivative of vitamin
A, were cloned. Since that time, there has been an explosion of new techniques
and concepts that have revealed how retinoic acid and its receptors regulate gene
expression at the molecular level and impact development and homeostasis. Some
of these new findings have been summarized in recent specialized reviews, but it
has been over 20 years since a comprehensive account of vitamin A function and
metabolism has been published (The Retinoids Biology, Chemistry and Medicine
edited by Sporn, Roberts and Goodman, Raven Press, New York 1993; Vitamin A
in Health and Disease, edited by Rune Blomhoff, Dekker, New York, 1994).
In view of the recent explosion in this field, it is timely to publish a contempo-
rary, comprehensive, book series recapitulating the most exciting developments in
the field and covering fundamental research in molecular mechanisms of vitamin
A action, its role in physiology, development, and continued well-being, and the
potential of vitamin A derivatives and synthetic mimetics to serve as therapeutic
treatments for cancers and other debilitating human diseases.
Here, we present the first volume of a multivolume series on Retinoic Acid
Signaling that will cover all aspects of this broad and diverse field. One aim
of Volume I is to present a compilation of topics related to the biochemistry of
nuclear retinoic acid receptors, from their architecture when bound to DNA
and associated with their coregulators to their ability to regulate target gene
v
vi Foreword
transcription. A second aim is to provide insight into recent advances that have
been made in identifying novel targets and nongenomic effects of retinoic acid.
Volume I is divided into ten chapters contributed by prominent experts in
their respective fields. Each chapter starts with the history of the area of research.
Then, the key findings that contributed to development of the field are described,
followed by a detailed look at key findings and progress that is being made in
current, ongoing research. Each chapter is concluded with a discussion of the rel-
evance of the research and a perspective on missing pieces and lingering gaps that
the authors recommend will be important in defining future directions in vitamin A
research.
The volume begins with a retrospective of the vitamin A story and of the clon-
ing of the nuclear retinoic acid receptors. Then, it is organized into three broad
areas. The first area focuses on fundamental research covering the architecture of
DNA bound RARs, the structural basis for coregulator interaction and exchange,
the evolution of the receptors, and the role of the RXR heterodimerization partner.
The second area addresses the complexity of the RAR mediated transcriptional
‐
regulatory programs, focusing on the epigenetic changes at the gene promoters
and on recent integrative genomics. The third area presents new mechanisms of
action of RARs, including nongenomic effects, novel targets, and microRNAs.
We thank all of the authors for their efforts in preparing this volume. They
comprehensively reviewed the literature and provided stimulating ideas that will
serve to guide continued development of the retinoid field. They pointed out many
questions that remain unsolved and noted that these answers will require new
state-of-the-art techniques.
We also thank and acknowledge Meran Owen for his invitation to put together
this “Retinoic Acid Signaling” book series, his assistant, Tanja van Gaans for her
constant help, and Springer Publishing for its support of this project.
It is our hope that this book will serve as an illuminating introduction to the fas-
cinating field of vitamin A biology for those who are not familiar with the amazing
molecular intricacies of retinoic acid signaling, as well as a frequent reference for
the current and next generations of scientists working in the field of retinoids and
nuclear receptors.
Mary Ann Asson-Batres
Cécile Rochette-Egly
Contents
1 History of Retinoic Acid Receptors ........................... 1
Doris M. Benbrook, Pierre Chambon, Cécile Rochette-Egly
and Mary Ann Asson-Batres
2 Architecture of DNA Bound RAR Heterodimers ................ 21
Natacha Rochel and Dino Moras
3 Retinoic Acid Receptors: Structural Basis for Coregulator
Interaction and Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Albane le Maire and William Bourguet
4 Evolution of Retinoic Acid Receptors and Retinoic
Acid Signaling............................................. 55
Juliana Gutierrez-Mazariegos, Michael Schubert and Vincent Laudet
5 RXRs: Collegial Partners ................................... 75
Federica Gilardi and Béatrice Desvergne
6 Nuclear and Extra-Nuclear Effects of Retinoid
Acid Receptors: How They Are Interconnected ................. 103
Aleksandr Piskunov, Ziad Al Tanoury and Cécile Rochette-Egly
7 The Roles of Retinoic Acid and Retinoic Acid Receptors
in Inducing Epigenetic Changes.............................. 129
Alison Urvalek, Kristian Bruun Laursen and Lorraine J. Gudas
8 RARs and MicroRNAs...................................... 151
Clara Nervi and Francesco Grignani
9 Integrative Genomics to Dissect Retinoid Functions ............. 181
Marco-Antonio Mendoza-Parra and Hinrich Gronemeyer
vii
viii Contents
10 Complexity of the RAR Mediated Transcriptional
‐
Regulatory Programs....................................... 203
Zhijie Liu, Qidong Hu and Michael G. Rosenfeld
Subject Index .................................................. 227
Chapter 1
History of Retinoic Acid Receptors
Doris M. Benbrook, Pierre Chambon, Cécile Rochette-Egly
and Mary Ann Asson-Batres
Abstract The discovery of retinoic acid receptors arose from research into how
vitamins are essential for life. Early studies indicated that Vitamin A was metabolized
into an active factor, retinoic acid (RA), which regulates RNA and protein expression
in cells. Each step forward in our understanding of retinoic acid in human health was
accomplished by the development and application of new technologies. Development
cDNA cloning techniques and discovery of nuclear receptors for steroid hormones pro-
vided the basis for identicfi ation of two classes of retinoic acid receptors, RARs and
RXRs, each of which has three isoforms, α, β and . DNA manipulation and crystal-
ɣ
lographic studies revealed that the receptors contain discrete functional domains respon-
sible for binding to DNA, ligands and cofactors. Ligand binding was shown to induce
conformational changes in the receptors that cause release of corepressors and recruit-
ment of coactivators to create functional complexes that are bound to consensus pro-
moter DNA sequences called retinoic acid response elements (RAREs) and that cause
D. M. Benbrook (*)
Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center,
975 NE 10th St BRC1374, Oklahoma City 73165, USA
e-mail: [email protected]
D. M. Benbrook
Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center,
975 NE 10th St BRC1374, Oklahoma City 73165, USA
P. Chambon · C. Rochette-Egly
IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), INSERM, U964,
CNRS, UMR7104, Université de Strasbourg, 1 rue Laurent Fries, BP 10142, 67404
Illkirch Cedex, France
e-mail: [email protected]
C. Rochette-Egly
e-mail: [email protected]
M. A. Asson-Batres
Department of Biological Sciences, Tennessee State University,
3500 John A Merritt Blvd, Nashville 37209, USA
e-mail: [email protected]
M. A. Asson-Batres and C. Rochette-Egly (eds.), The Biochemistry of Retinoic Acid Receptors I: 1
Structure, Activation, and Function at the Molecular Level, Subcellular Biochemistry 70,
DOI: 10.1007/978-94-017-9050-5_1, © Springer Science+Business Media Dordrecht 2014
2 D. M. Benbrook et al.
opening of chromatin and transcription of adjacent genes. Homologous recombination
technology allowed the development of mice lacking expression of retinoic acid recep-
tors, individually or in various combinations, which demonstrated that the receptors
exhibit vital, but redundant, functions in fetal development and in vision, reproduction,
and other functions required for maintenance of adult life. More recent advancements
in sequencing and proteomic technologies reveal the complexity of retinoic acid recep-
tor involvement in cellular function through regulation of gene expression and kinase
activity. Future directions will require systems biology approaches to decipher how
these integrated networks affect human stem cells, health, and disease.
Abbreviations
ChIP Chromatin immunoprecipitation
ChIP-seq Chromatin immunoprecipitation coupled with deep sequencing
cDNA Complementary DNA
CRABP Cellular retinoic acid binding protein
CRBP Cellular retinol binding protein
DNA Deoxyribonucleic acid
DBD DNA binding domain
LBD Ligand binding domain
NMR Nuclear magnetic resonance
RA Retinoic acid
RAR Retinoic acid receptor
RARE Retinoic acid response element
RNA Ribonucleic acid
RNA-seq High throughput RNA sequencing
RXR Retinoic X receptor
VAD Vitamin A deficiency
Introduction: In Quest of
a Mechanism of Action for Vitamin A
The idea that essential factors other than proteins, fat, starch, sugar, or min-
erals are present in food was a novel concept before the late 1880s. Ultimately
this notion was verified by a series of human dietary supplementation studies
and controlled experiments in animal models conducted between 1880 and 1920,
which demonstrated that removal of these factors from the diet caused debilitat-
ing illnesses and death. The first discoveries in the field were made by Christiaan
Eijkman and Frederick Gowland Hopkins who found that rice polishings con-
tain substances preventing beriberi. These investigators received the Nobel prize
for their work in 1929 [17]. In 1912, Casimer Funk identified the active fraction,