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Integrative Genomics to Dissect Retinoid Functions

  • Marco-Antonio Mendoza-Parra
  • Hinrich Gronemeyer
Part of the Subcellular Biochemistry book series (SCBI, volume 70)

Abstract

Retinoids and rexinoids, as all other ligands of the nuclear receptor (NR) family, act as ligand-regulated trans-acting transcription factors that bind to cis-acting DNA regulatory elements in the promoter regions of target genes (for reviews see [12, 22, 23, 26, 36]). Ligand binding modulates the communication functions of the receptor with the intracellular environment, which essentially entails receptor-protein and receptor-DNA or receptor-chromatin interactions. In this communication network, the receptor simultaneously serves as both intracellular sensor and regulator of cell/organ functions. Receptors are “intelligent” mediators of the information encoded in the chemical structure of a nuclear receptor ligand, as they interpret this information in the context of cellular identity and cell-physiological status and convert it into a dynamic chain of receptor-protein and receptor-DNA interactions. To process input and output information, they are composed of a modular structure with several domains that have evolved to exert particular molecular recognition functions. As detailed in other chapters in this volume, the main functional domains are the DNA-binding (DBD) and ligand-binding (LBD) [5, 6, 7, 38, 56, 71]. The LBD serves as a dual input-output information processor. Inputs, such as ligand binding or receptor phosphorylations, induce allosteric changes in receptor surfaces that serve as docking sites for outputs, such as subunits of transcription and epigenetic machineries or enzyme complexes. The complexity of input and output signals and their interdependencies is far from being understood.

Keywords

Retinoic Acid Retinoic Acid Receptor Massive Parallel Sequencing Retinoic Acid Signaling Cell Fate Transition 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

9-cis RA

9-cis retinoid acid

AM580

RARα-selective synthetic ligand

apoNR

Non-liganded NR

at-RA

All-trans retinoic acid

BMS753

RARα-selective synthetic ligand

BMS961

RARγ-selective synthetic ligand

CD437

RARγ-selective synthetic ligand

Cistrome

The total set of genes in a given cell that contains cis-acting DNA binding/response/target sites for a given TF; generally defined by ChIP-seq and related technologies

ChIP

Chromatin immunoprecipitation

ChIP-seq

ChIP coupled to massive parallel sequencing

CoA

Co-activator

CoR

Co-repressor

DBD

DNA-binding domain

ECC

Embryo carcinoma cell (e.g., F9 or P19)

ESC

Embryonic stem cells

Epigenome

General term to describe the patterns of post-translational modification of chromatin histones alone the genome and the modification of DNA, such as methylation or hydroxymethylation of cytosines

HDAC

Histone deacetylase

IP

Immunoprecipitation

IPed

Immunoprecipitated

Isotype

Three RAR and RXR receptors expressed from distinct genes (RARα, RARβ RARγ; RXRα, RXRβ and RXRγ)

LBD

Ligand-binding domain

MEF

Mouse embryonic fibroblast

NR

Nuclear receptor

RAR α, β, γ

Retinoic acid receptor α, β, γ

RXR α, β, γ

Retinoid X receptor α, β, γ

TF

Transcription factor

Transcriptome

All transcribed RNAs produced in one or a population of cells.

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© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Marco-Antonio Mendoza-Parra
    • 1
  • Hinrich Gronemeyer
    • 1
  1. 1.Department of Functional Genomics and CancerInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS, INSERM, Université de StrasbourgIllkirch CedexFrance

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