Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3',5'-Cyclic-AMP Phosphodiesterases / chemistry*
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3',5'-Cyclic-AMP Phosphodiesterases / genetics
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Activating Transcription Factor 1
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Binding Sites
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Cell Separation
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Chromatin / chemistry*
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Chromatin / metabolism
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Cyclic AMP / metabolism
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Cyclic AMP-Dependent Protein Kinases / chemistry
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Cyclic AMP-Dependent Protein Kinases / metabolism*
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DNA / chemistry
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Dimerization
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Flow Cytometry
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Gene Expression Regulation, Fungal*
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Genotype
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MAP Kinase Signaling System*
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Models, Genetic
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Mutation
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Nitrogen / chemistry
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Phosphoproteins / metabolism
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Phosphoproteins / physiology*
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Promoter Regions, Genetic
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Protein Binding
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Reverse Transcriptase Polymerase Chain Reaction
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Schizosaccharomyces / enzymology*
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Schizosaccharomyces pombe Proteins / chemistry*
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Schizosaccharomyces pombe Proteins / genetics
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Schizosaccharomyces pombe Proteins / metabolism
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Schizosaccharomyces pombe Proteins / physiology*
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Signal Transduction
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Transcriptional Activation
Substances
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Activating Transcription Factor 1
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Cgs2 protein, S pombe
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Chromatin
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Phosphoproteins
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Schizosaccharomyces pombe Proteins
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atf1 protein, S pombe
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DNA
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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3',5'-Cyclic-AMP Phosphodiesterases
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Nitrogen