Linked Life Data

21276787

Source:http://linkedlifedata.com/resource/pubmed/id/21276787

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-3-7
pubmed:abstractText
RA receptors (RARs) have been thought to function through a binary repressor-activator mechanism: in the absence of ligand, they function as transcriptional repressors, and, in the presence of ligand, they function as transcriptional activators. This prevailing model of RAR mechanism has been derived mostly from in vitro studies and has not been widely tested in developmental contexts. Here, we investigate whether zebrafish RARs function as transcriptional activators or repressors during early embryonic anterior-posterior patterning. Ectopic expression of wild-type zebrafish RARs does not disrupt embryonic patterning and does not sensitize embryos to RA treatment, indicating that RAR availability is not limiting in the embryo. In contrast, ectopic expression of hyperactive zebrafish RARs induces expression of a RA-responsive reporter transgene as well as ectopic expression of endogenous RA-responsive target genes. However, ectopic expression of dominant negative zebrafish RARs fails to induce embryonic phenotypes that are consistent with loss of RA signaling, despite their ability to function as transcriptional repressors in heterologous cell culture assays. Together, our studies suggest that zebrafish RAR function is context-dependent and that, during early patterning, zebrafish RARs function primarily as transcriptional activators and may only have minimal ability to act as transcriptional repressors. Thus, it seems that the binary model for RAR function does not apply to all in vivo scenarios. Taking into account studies of RA signaling in tunicates and tetrapods, we propose a parsimonious model of the evolution of RAR function during chordate anterior-posterior patterning.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1095-564X
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
352
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
128-40
pubmed:dateRevised
2011-11-3
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Zebrafish retinoic acid receptors function as context-dependent transcriptional activators.
pubmed:affiliation
Developmental Genetics Program and Department of Cell Biology, Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, 10016, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural