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Snf1--a Histone Kinase That Works in Concert with the Histone Acetyltransferase Gcn5 to Regulate Transcription
Wan-Sheng Lo,1Laura Duggan,1N.
C. Tolga ,Emre,1Rimma Belotserkovskya,1William S. Lane,2Ramin Shiekhattar,1Shelley L. Berger1*
Modification of histones is an important element in the regulation
of gene expression. Previous work suggested a link betweenacetylation
and phosphorylation, but questioned its mechanisticbasis. We
have purified a histone H3 serine-10 kinase complexfrom
Saccharomyces cerevisiae and have identified its catalyticsubunit as Snf1. The Snf1/AMPK family of kinases function in conservedsignal transduction pathways. Our results show that Snf1 and theacetyltransferase Gcn5 function in an obligate sequence to enhanceINO1 transcription by modifying histone H3 serine-10 and
lysine-14.Thus, phosphorylation and acetylation are
targeted to the samehistone by promoter-specific regulation by a
kinase/acetyltransferasepair, supporting models of gene regulation
wherein transcriptionis controlled by coordinated patterns of histone
modification.
1 Molecular Genetics Program, The Wistar
Institute, Philadelphia, PA 19104, USA.
2 Harvard
Microchemistry and Proteomics Analysis Facility, Harvard University,
Cambridge, MA 02138, USA.
*
To whom correspondence should be addressed at The Wistar
Institute, 3601 Spruce Street, Room 389, Philadelphia, PA 19104,USA.
E-mail: berger{at}wistar.upenn.edu
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