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dictyNews Volume 32 Number 07
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.
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Abstracts
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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]
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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]
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[End dictyNews, volume 32, number 7]
