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.
Citation
Linney, E., Donerly, S., Mackey, L., and Dobbs-McAuliffe, B. (2011) The negative side of retinoic acid receptors. Neurotoxicology and teratology. 33(6):631-40.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping