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Originally published In Press as doi:10.1074/jbc.M409079200 on September 23, 2004

J. Biol. Chem., Vol. 279, Issue 49, 50857-50863, December 3, 2004
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Atf1-Pcr1-M26 Complex Links Stress-activated MAPK and cAMP-dependent Protein Kinase Pathways via Chromatin Remodeling of cgs2+*

Mari K. Davidson{ddagger}, Harish K. Shandilya{ddagger}, Kouji Hirota§, Kunihiro Ohta§, and Wayne P. Wahls{ddagger}

From the {ddagger}Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205 and the §Genetic Dynamics Research Unit Laboratory, The Institute of Physical and Chemical Research, Wako, Saitama 351-0198, Japan

Although co-ordinate interaction between different signal transduction pathways is essential for developmental decisions, interpathway connections are often obscured and difficult to identify due to cross-talk. Here signals from the fission yeast stress-activated MAPK Spc1 are shown to regulate Cgs2, a negative regulator of the cAMP-dependent protein kinase (protein kinase A) pathway. Pathway integration is achieved via Spc1-dependent binding of Atf1-Pcr1 heterodimer to an M26 DNA site in the cgs2+ promoter, which remodels chromatin to regulate expression of cgs2+ and targets downstream of protein kinase A. This direct interpathway connection co-ordinates signals of nitrogen and carbon source depletion to affect a G0 cell-cycle checkpoint and sexual differentiation. The Atf1-Pcr1-M26 complex-dependent chromatin remodeling provides a molecular mechanism whereby Atf1-Pcr1 heterodimer can function differentially as either a transcriptional activator, or as a transcriptional repressor, or as an inducer of meiotic recombination. We also show that the Atf1-Pcr1-M26 complex functions as both an inducer and repressor of chromatin remodeling, which provides a way for various chromatin remodeling-dependent effector functions to be regulated.


Received for publication, August 9, 2004 , and in revised form, September 7, 2004.

* This study was supported by Grants GM62244 and GM62801 from the NIGMS, National Institutes of Health. Additional support was provided by the Bioarchitect Research Program of The Institute of Physical and Chemical Research and the Core Research for Evolutional Science and Technology of Japan Science and Technology Corporation, and the Ministry of Education, Science, Culture & Sports, Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, 4301 W. Markham Street (slot 516), Little Rock, AR 72205-7199. Tel.: 501-686-5787; Fax: 501-526-7008; E-mail: wahlswaynep{at}uams.edu.


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