Snf1--a histone kinase that works in concert with the histone acetyltransferase Gcn5 to regulate transcription.
Modification of histones is an important element in the regulation of gene expression. Previous work suggested a link between acetylation and phosphorylation, but questioned its mechanistic basis. We have purified a histone H3 serine-10 kinase complex from Saccharomyces cerevisiae and have identified its catalytic subunit as Snf1. The Snf1/AMPK family of kinases function in conserved signal transduction pathways. Our results show that Snf1 and the acetyltransferase Gcn5 function in an obligate sequence to enhance INO1 transcription by modifying histone H3 serine-10 and lysine-14. Thus, phosphorylation and acetylation are targeted to the same histone by promoter-specific regulation by a kinase/acetyltransferase pair, supporting models of gene regulation wherein transcription is controlled by coordinated patterns of histone modification.
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Molecular Genetics Program, The Wistar Institute, Philadelphia, PA 19104, USA.
Duggan
L
L
Emre
N C
NC
Belotserkovskya
R
R
Lane
W S
WS
Shiekhattar
R
R
Berger
S L
SL
D000107:Acetylation; D020134:Catalytic Domain; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D007296:Myo-Inositol-1-Phosphate Synthase / Q000235:genetics; D009707:Nucleosomes / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000302:isolation & purification / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D015533:Transcriptional Activation; D000099224:p300-CBP-Associated Factor
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D051548:Histone Acetyltransferases; D006657:Histones; D008239:Lysine; D007296:Myo-Inositol-1-Phosphate Synthase; D009707:Nucleosomes; D010768:Phosphoserine; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor; C071570:SNF1-related protein kinases