Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
2010-11-8
pubmed:abstractText
The mammalian clock is regulated at the cellular level by a transcriptional/translational feedback loop. BMAL1/clock (or NPAS2) heterodimers activate the expression of the period (PER) and cryptochrome (CRY) genes acting as transcription factors directed to the PER and CRY promoters via E-box elements. PER and CRY proteins form heterodimers and suppress the activity of the BMAL1/clock (or NPAS2) completing the feedback loop. The circadian expression of BMAL1 is influenced by retinoic acid receptor-related orphan receptor ? (ROR?) and REV-ERB?, two nuclear receptors that target a ROR-response element in the promoter of the BMAL1 gene. Given that BMAL1 functions as an obligate heterodimer with either clock or NPAS2, it is unclear how the expression of the partner is coordinated with BMAL1 expression. Here, we demonstrate that NPAS2 is also a ROR? and REV-ERB? target gene. Using a ChIP/microarray screen, we identified both ROR? and REV-ERB? occupancy of the NPAS2 promoter. We identified two functional ROREs within the NPAS2 promoter and also demonstrate that both ROR? and REV-ERB? regulate the expression of NPAS2 mRNA. These data suggest a mechanism by which ROR? and REV-ERB? coordinately regulate the expression of the positive arm of the circadian rhythm feedback loop.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
12
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35386-92
pubmed:dateRevised
2011-11-14
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Characterization of the core mammalian clock component, NPAS2, as a REV-ERBalpha/RORalpha target gene.
pubmed:affiliation
The Scripps Research Institute, Jupiter, Florida 33458, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural