PUBLICATION

The negative side of retinoic acid receptors

Authors
Linney, E., Donerly, S., Mackey, L., and Dobbs-McAuliffe, B.
ID
ZDB-PUB-110721-4
Date
2011
Source
Neurotoxicology and teratology   33(6): 631-40 (Review)
Registered Authors
Dobbs-McAuliffe, Betsy, Donerly, Sue, Linney, Elwood
Keywords
none
MeSH Terms
  • Animals
  • Embryo, Nonmammalian/drug effects*
  • Embryo, Nonmammalian/enzymology
  • Embryo, Nonmammalian/metabolism
  • Epigenesis, Genetic/drug effects
  • Gene Expression Regulation, Developmental/drug effects*
  • Receptors, Retinoic Acid/genetics*
  • Response Elements/drug effects
  • Response Elements/genetics
  • Tretinoin/toxicity*
  • Zebrafish/embryology*
  • Zebrafish/genetics
PubMed
21767634 Full text @ Neurotoxicol. Teratol.
Abstract
This is a review of research that supports a hypothesis regarding early restriction of gene expression in the 21 vertebrate embryo. We hypothesize that vertebrate retinoic acid receptors (RARs for several vertebrates but 22 rars for zebrafish) are part of an embryonic, epigenetic switch whose default position, at the time of 23 fertilization is "OFF". This is due to the assemblage of a rar-corepressor-histone deacetylase complex on 24 retinoic acid response elements (RAREs) in regulatory regions of a subset of genes. In addition, selective and 25 precise allocation of retinoic acid during early development through the interaction of Phase I enzymes 26 throws the switch "ON" in a predictable, developmental manner. We are proposing that this is a basic, early 27 embryonic switch that can cause the initiation of cascades of gene expression that are responsible for at least 28 some early, diversification of cell phenotypes. Dehydrogenases and a subset of cytochrome p450 genes 29 (cyp26a1, cyp26b1, and cyp26c1) play the major role in providing the retinoic acid and limiting its access. We 30 also suggest that this mechanism may be playing a significant role in the repression of genes in 31 undifferentiated stem cells.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping