Retinoic Acid Receptor Coregulators in Epigenetic Regulation of Target Genes

New Insights Into the Roles of Retinoic Acid Signaling in Nervous System Development and the Establishment of Neurotransmitter Systems

“…extensively (Rochette-Egly, 2015;Samarut and Rochette-Egly, 2012;Wei, 2015), the versatile modes of RXR action are less well understood (Ahuja et al, 2003;Evans and Mangelsdorf, 2014;Germain et al, 2002;Lefebvre et al, 2010). In mammals, three RARs (α, β and γ) and three RXRs (α, β and γ) have been identified, which…”

“…show diverse expression patterns as well as divergent functions and are believed to associate into more than 30 different RAR/RXR heterodimers that transduce signals in the presence of all-trans RA (Gutierrez-Mazariegos et al, 2014b;Mark et al, 2009;Samarut and Rochette-Egly, 2012;. The highly gene-specific transcriptional responses to RAR-mediated RA signals are further based upon a plethora of co-regulators as well as on the placement or removal of epigenetic marks on histones or on DNA (Gudas, 2013;Wei, 2015).…”

“…Many other genes that facilitate cell cycle exit or inhibit the proliferation of neural progenitors can be regulated through either direct or indirect mechanisms of RA signaling, but often require specific developmental conditions (Janesick et al, 2015). Highly cell-and gene-specific transcriptional responses to RA are mediated by numerous coregulators, by the placement or removal of epigenetic marks as well as through a number of alternative RAR-independent signaling pathways (Carvalho and Schubert, 2013;Gudas, 2013;Wei, 2015). For instance, RA signals can determine the precise timing of stem cell differentiation by generating heritable epigenetic changes in chromatin responsiveness to both retinoid and other signaling pathways (Gudas, 2013) and exert pleiotropic effects on cell survival and cell cycle, depending on the presence of specific binding proteins (Schug et al, 2007;Wolf, 2008).…”

CYP26A1 gene promoter is a useful tool for reporting RAR-mediated retinoid activity

“…Retinoic acid (RA), a major active metabolite of vitamin A, functions as a pan-agonist ligand of nuclear retinoic acid receptors (RARα, β, and γ), which partner with retinoid X receptors (RXRα, β, and γ) and bind specifically to retinoic acid response elements (RARE) in target genes [1][2][3][4]. The canonical RARE consists of a core of two hexameric motifs of PuG(G/T)TCA(X) n PuG(G/T)TCA, generally oriented as a direct repeat (DR) spaced by two or five nucleotides (called DR2 or DR5).…”