000030457 001__ 30457 000030457 005__ 20150420164418.0 000030457 0248_ $$aoai:doc.rero.ch:20121010113539-PD$$punifr$$ppostprint$$prero_explore$$particle$$zthesis_urn$$zcdu57$$zreport$$zthesis$$zbook$$zjournal$$zcdu16$$zpreprint$$zcdu1$$zdissertation$$zcdu34 000030457 041__ $$aeng 000030457 080__ $$a57 000030457 100__ $$aKowalska, Elzbieta$$uInstitute of Pharmacology and Toxicology, University of Zurich, Switzerland 000030457 245__ $$9eng$$aDistinct roles of DBHS family members in the circadian transcriptional feedback loop 000030457 269__ $$c2012-09-10 000030457 520__ $$9eng$$aFactors interacting with core circadian clock components are essential to achieve transcriptional feedback necessary for metazoan clocks. Here we show that all three members of the Drosophila Behavior Human Splicing (DBHS) family of RNA-binding proteins play a role in the mammalian circadian oscillator, abrogating or altering clock function when overexpressed or depleted in cells. Although these proteins are members of so-called nuclear paraspeckles, depletion of paraspeckles themselves via silencing of the structural non-coding RNA (ncRNA) Neat1 did not affect overall clock function, suggesting that paraspeckles are not required for DBHS-mediated circadian effects. Instead, we show that the proteins bound to circadian promoter DNA in a fashion that required the PERIOD (PER) proteins, and potently repressed E box-mediated transcription but not CMV promoter-mediated transcription when exogenously recruited. Nevertheless, mice with one or both copies of these genes deleted show only small changes in period length or clock gene expression in vivo. Data from transient transfections show that each of these proteins can either repress or activate depending on the context. Taken together, our data suggest that all of the DBHS family members serve overlapping or redundant roles as transcriptional cofactors at circadian clock-regulated genes. 000030457 700__ $$aRipperger, Jürgen A.$$uDepartment of Biology, Unit for Biochemistry, University of Fribourg, Switzerland 000030457 700__ $$aMuheim, Christine$$uInstitute of Pharmacology and Toxicology, University of Zurich, Switzerland 000030457 700__ $$aMaier, Bert$$uLaboratory of Chronobiology, Institute of Medical Immunology, Charite Universitätsmedizin, Berlin, Germany 000030457 700__ $$aKurihara, Yasuyuki$$uDepartment of Natural Environment and Information, Yokohama National University, Japan 000030457 700__ $$aFox, Archa H.$$uWestern Australian Institute for Medical Research and Centre For Medical Research, University of Western Australia, Crawley Australia 000030457 700__ $$aKramer, Achim$$uLaboratory of Chronobiology, Institute of Medical Immunology, Charite Universitätsmedizin, Berlin, Germany 000030457 700__ $$aBrown, Steven A.$$uInstitute of Pharmacology and Toxicology, University of Zurich, Switzerland 000030457 773__ $$g2012///-$$tMolecular and Cellular Biology 000030457 775__ $$gPublished version$$ohttp://dx.doi.org/10.1128/MCB.00334-12 000030457 8564_ $$frip_drd.pdf$$qapplication/pdf$$s1771692$$uhttps://doc.rero.ch/record/30457/files/rip_drd.pdf$$yorder:1$$zpdf 000030457 918__ $$aFaculté des sciences$$bDécanat, Ch. du Musée 6A, 1700 Fribourg$$cBiologie 000030457 919__ $$aUniversité de Fribourg$$bFribourg$$ddoc.support@rero.ch 000030457 980__ $$aPOSTPRINT$$bUNIFR$$fART_JOURNAL 000030457 990__ $$a20121010113539-PD