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dc.contributor.authorLing, Jinli
dc.contributor.authorDubruille, Raphaelle
dc.contributor.authorEmery, Patrick
dc.date2022-08-11T08:09:29.000
dc.date.accessioned2022-08-23T16:32:21Z
dc.date.available2022-08-23T16:32:21Z
dc.date.issued2012-11-21
dc.date.submitted2013-01-23
dc.identifier.citationJ Neurosci. 2012 Nov 21;32(47):16959-70. doi: 10.1523/JNEUROSCI.1888-12.2012. <a href="http://dx.doi.org/10.1523/JNEUROSCI.1888-12.2012" target="_blank">Link to article on publisher's site</a>
dc.identifier.issn0270-6474 (Linking)
dc.identifier.doi10.1523/JNEUROSCI.1888-12.2012
dc.identifier.pmid23175847
dc.identifier.urihttp://hdl.handle.net/20.500.14038/37866
dc.description<p>First author Jinli Ling is a doctoral student in the Neuroscience Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.</p>
dc.description.abstractCircadian rhythms are generated by well-conserved interlocked transcriptional feedback loops in animals. In Drosophila, the dimeric transcription factor CLOCK/CYCLE (CLK/CYC) promotes period (per), timeless (tim), vrille (vri), and PAR-domain protein 1 (Pdp1) transcription. PER and TIM negatively feed back on CLK/CYC transcriptional activity, whereas VRI and PDP1 negatively and positively regulate Clk transcription, respectively. Here, we show that the alpha isoform of the Drosophila FOS homolog KAYAK (KAY) is required for normal circadian behavior. KAY-alpha downregulation in circadian pacemaker neurons increases period length by 1.5 h. This behavioral phenotype is correlated with decreased expression of several circadian proteins. The strongest effects are on CLK and the neuropeptide PIGMENT DISPERSING FACTOR, which are both under VRI and PDP1 control. Consistently, KAY-alpha can bind to VRI and inhibit its interaction with the Clk promoter. Interestingly, KAY-alpha can also repress CLK activity. Hence, in flies with low KAY-alpha levels, CLK derepression would partially compensate for increased VRI repression, thus attenuating the consequences of KAY-alpha downregulation on CLK targets. We propose that the double role of KAY-alpha in the two transcriptional loops controlling Drosophila circadian behavior brings precision and stability to their oscillations.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23175847&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1523/JNEUROSCI.1888-12.2012
dc.rightsPublisher PDF posted as allowed by the publisher's author rights policy at http://www.jneurosci.org/site/misc/ifa_policies.xhtml#copyright.
dc.subjectDrosophila
dc.subjectCircadian Rhythm
dc.subjectDrosophila Proteins
dc.subjectBiological Clocks
dc.subjectFeedback, Physiological
dc.subjectNeurons
dc.subjectTranscription, Genetic
dc.subjectBehavioral Neurobiology
dc.titleKAYAK-alpha modulates circadian transcriptional feedback loops in Drosophila pacemaker neurons
dc.typeJournal Article
dc.source.journaltitleThe Journal of neuroscience : the official journal of the Society for Neuroscience
dc.source.volume32
dc.source.issue47
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1136&amp;context=neurobiology_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/neurobiology_pp/137
dc.identifier.contextkey3608531
refterms.dateFOA2022-08-23T16:32:21Z
html.description.abstract<p>Circadian rhythms are generated by well-conserved interlocked transcriptional feedback loops in animals. In Drosophila, the dimeric transcription factor CLOCK/CYCLE (CLK/CYC) promotes period (per), timeless (tim), vrille (vri), and PAR-domain protein 1 (Pdp1) transcription. PER and TIM negatively feed back on CLK/CYC transcriptional activity, whereas VRI and PDP1 negatively and positively regulate Clk transcription, respectively. Here, we show that the alpha isoform of the Drosophila FOS homolog KAYAK (KAY) is required for normal circadian behavior. KAY-alpha downregulation in circadian pacemaker neurons increases period length by 1.5 h. This behavioral phenotype is correlated with decreased expression of several circadian proteins. The strongest effects are on CLK and the neuropeptide PIGMENT DISPERSING FACTOR, which are both under VRI and PDP1 control. Consistently, KAY-alpha can bind to VRI and inhibit its interaction with the Clk promoter. Interestingly, KAY-alpha can also repress CLK activity. Hence, in flies with low KAY-alpha levels, CLK derepression would partially compensate for increased VRI repression, thus attenuating the consequences of KAY-alpha downregulation on CLK targets. We propose that the double role of KAY-alpha in the two transcriptional loops controlling Drosophila circadian behavior brings precision and stability to their oscillations.</p>
dc.identifier.submissionpathneurobiology_pp/137
dc.contributor.departmentGraduate School of Biomedical Sciences, Neuroscience Program
dc.contributor.departmentEmery Lab
dc.contributor.departmentNeurobiology
dc.source.pages16959-70
dc.contributor.studentJinli Ling
dc.description.thesisprogramNeuroscience


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