dictyNews Electronic Edition Volume 32, number 7 March 13, 2009 Please submit abstracts of your papers as soon as they have been accepted for publication by sending them to dicty@northwestern.edu or by using the form at http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit. Back issues of dictyNews, the Dicty Reference database and other useful information is available at dictyBase - http://dictybase.org. ========= Abstracts ========= The carboxy-terminal domain of Dictyostelium C-module-binding factor is an independent gene regulatory entity J. Lucas (1), A. Bilzer (1), L. Moll (2), I. Zündorf (3), T. Dingermann (3), L. Eichinger (2), O. Siol (1), T. Winckler (1) (1) School of Biology and Pharmacy, Institute of Pharmacy, Department of PharmaceuticalBiology, University of Jena, Semmelweisstrasse 10, 07743 Jena, Germany (2) Institute for Biochemistry I, Medical Faculty, University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany (3) Institute of Pharmaceutical Biology, University of Frankfurt, Max-von-Laue-Strasse 9, 60438 Frankfurt am Main, Germany PLoS ONE, in press The C-module-binding factor (CbfA) is a multidomain protein that belongs to  the family of jumonji-type (JmjC) transcription regulators. In the social  amoeba Dictyostelium discoideum, CbfA regulates gene expression during the  unicellular growth phase and multicellular development. CbfA and a related  D. discoideum CbfA-like protein, CbfB, share a paralogous domain arrangement  that includes the JmjC domain, presumably a chromatin-remodeling activity,  and two zinc finger-like (ZF) motifs. On the other hand, the CbfA and CbfB  proteins have completely different carboxy-terminal domains, suggesting  that the plasticity of such domains may have contributed to the adaptation  of the CbfA-like transcription factors to the rapid genome evolution in the  dictyostelid clade. To support this hypothesis we performed DNA microarray  and real-time RT-PCR measurements and found that CbfA regulates at least  160 genes during the vegetative growth of D. discoideum cells. Functional  annotation of these genes revealed that CbfA predominantly controls the  expression of gene products involved in housekeeping functions, such as  carbohydrate, purine nucleoside/nucleotide, and amino acid metabolism.  The CbfA protein displays two different mechanisms of gene regulation. The  expression of one set of CbfA-dependent genes requires at least the  JmjC/ZF domain of the CbfA protein and thus may depend on chromatin  modulation. Regulation of the larger group of genes, however, does not  depend on the entire CbfA protein and requires only the carboxyterminal  domain of CbfA (CbfA-CTD). An AT-hook motif located in CbfA-CTD, which  is known to mediate DNA binding to A+T-rich sequences in vitro, contributed to CbfA-CTD-dependent gene regulatory functions in vivo. Submitted by: Thomas Winckler [t.winckler@uni-jena.de] -------------------------------------------------------------------------------- The mood stabiliser lithium suppresses PIP3 signalling in Dictyostelium and human cells Jason S. King, Regina Teo, Jonathan Ryves, Jonathan V. Reddy, Owen Peters, Ben Orabi, Oliver Hoeller, Robin S. B. Williams2 and Adrian J. Harwood Disease Models & Mechanisms, in press Bipolar mood disorder (manic depression) is a major psychiatric disorder whose molecular origins are unknown. Mood stabilisers offer patients both acute and prophylactic treatment, and experimentally, they provide a means to probe the underlying biology of the disorder. Lithium and other mood stabilisers deplete intracellular inositol and it has been proposed that bipolar mood disorder arises from aberrant inositol (1,4,5)-trisphosphate [IP3, also known as Ins(1,4,5)P3] signalling. However, there is no definitive evidence to support this or any other proposed target; a problem exacerbated by a lack of good cellular models. Phosphatidylinositol (3,4,5)-trisphosphate [PIP3, also known as PtdIns(3,4,5)P3] is a prominent intracellular signal molecule within the central nervous system (CNS) that regulates neuronal survival, connectivity and synaptic function. By using the genetically tractable organism Dictyostelium, we show that lithium suppresses PIP3-mediated signalling. These effects extend to the human neutrophil cell line HL60. Mechanistically, we show that lithium attenuates  phosphoinositide synthesis and that its effects can be reversed by  overexpression of inositol monophosphatase (IMPase), consistent with  the inositol-depletion hypothesis. These results demonstrate a lithium  target that is compatible with our current knowledge of the genetic  predisposition for bipolar disorder. They also suggest that lithium therapy  might be beneficial for other diseases caused by elevated PIP3 signalling. Submitted by: Adrian Harwood [harwoodaj@cf.ac.uk] ============================================================== [End dictyNews, volume 32, number 7]