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C. Rochette-Egly
ChIp-Chip
ChIP-on-chip
ChIP-seq
ChIP coupled to massive parallel sequencing
DNA-chip
DNA microarrays
ECC
Embryonal carcinoma cell
ESC
Embryonic Stem Cell
KO
Knock Out
NGS
Next Generation Sequencing
PCR
Polymerase Chain Reaction
RT-PCR
Reverse Transcriptase PCR
qPCR
Quantitative PCR
RNA-seq
RNA sequencing (whole transcriptome sequencing using NGS)
RA
Retinoic Acid
RAR
Retinoic Acid Receptor
RARE
Retinoic Acid Response Element
RXR
Retinoid X Receptor
TF
Transcription factor
Transcriptome All transcribed RNAs produced in one or a population of cells
VAD
Vitamin A deficiency
WT
Wild Type
Introduction
Retinoic acid (RA), one of the major natural active metabolite of vitamin A (VA) is
well known to play critical roles during embryonic development through the regulation of cell differentiation and proliferation. Historically, the understanding of the
molecular mechanism of RA action was rapidly advanced when RA nuclear receptors
(RARs and RXRs) were cloned and characterized, and the consensus DNA retinoic
acid response elements (RAREs) present in target genes were identified (Benbrook
et al. 2014; Chambon 1996). This has led to the concept that RA is a ligand that binds
and activates RAR/RXR heterodimers, that, in turn to function as ligand-dependent
transcription factors (TFs) regulate the expression of target genes involved in cell
growth and differentiation (Rochette-Egly and Germain 2009). Numerous molecular
and structural studies have provided a plethora of information about the sequence of
events that initially follow RA binding (Al Tanoury et al. 2013).
However, understanding development requires a more comprehensive view of
the regulatory events mediated by RA at the molecular level. Therefore, several
laboratories have focused on dissecting RA-regulated gene programs during the RAinduced differentiation of embryonal carcinoma cells (ECCs) and embryonic stem
cells (ESCs). The first RA-regulated genes were identified in the early 1990s using
standard genetics/molecular biology approaches. More recently, the development of
hybridization-based microarray technology and high performance software analysis
programs, have allowed the characterization of hundreds of genes that are regulated
C. Rochette-Egly
ChIp-Chip
ChIP-on-chip
ChIP-seq
ChIP coupled to massive parallel sequencing
DNA-chip
DNA microarrays
ECC
Embryonal carcinoma cell
ESC
Embryonic Stem Cell
KO
Knock Out
NGS
Next Generation Sequencing
PCR
Polymerase Chain Reaction
RT-PCR
Reverse Transcriptase PCR
qPCR
Quantitative PCR
RNA-seq
RNA sequencing (whole transcriptome sequencing using NGS)
RA
Retinoic Acid
RAR
Retinoic Acid Receptor
RARE
Retinoic Acid Response Element
RXR
Retinoid X Receptor
TF
Transcription factor
Transcriptome All transcribed RNAs produced in one or a population of cells
VAD
Vitamin A deficiency
WT
Wild Type
Introduction
Retinoic acid (RA), one of the major natural active metabolite of vitamin A (VA) is
well known to play critical roles during embryonic development through the regulation of cell differentiation and proliferation. Historically, the understanding of the
molecular mechanism of RA action was rapidly advanced when RA nuclear receptors
(RARs and RXRs) were cloned and characterized, and the consensus DNA retinoic
acid response elements (RAREs) present in target genes were identified (Benbrook
et al. 2014; Chambon 1996). This has led to the concept that RA is a ligand that binds
and activates RAR/RXR heterodimers, that, in turn to function as ligand-dependent
transcription factors (TFs) regulate the expression of target genes involved in cell
growth and differentiation (Rochette-Egly and Germain 2009). Numerous molecular
and structural studies have provided a plethora of information about the sequence of
events that initially follow RA binding (Al Tanoury et al. 2013).
However, understanding development requires a more comprehensive view of
the regulatory events mediated by RA at the molecular level. Therefore, several
laboratories have focused on dissecting RA-regulated gene programs during the RAinduced differentiation of embryonal carcinoma cells (ECCs) and embryonic stem
cells (ESCs). The first RA-regulated genes were identified in the early 1990s using
standard genetics/molecular biology approaches. More recently, the development of
hybridization-based microarray technology and high performance software analysis
programs, have allowed the characterization of hundreds of genes that are regulated