The Republican Kinase Cdc7 Marks Histones to Regulate The Transcription of Biosynthesis Genes and DNA Replication

II Post-translational histone modifications (PTMs) play important roles in regulating various DNA-templated cellular functions. Histone H3 Threonine 45 phosphorylation (H3T45P) is a modification that is enriched during S-phase of the cell cycle in Saccharomyces cerevisiae and is carried out by the DNA-replication kinase Cdc7-Dbf4 (DDK) in vivo and in vitro. To understand the function of this mark we identified the genomic H3T45P locations by performing chromatin immunoprecipitation followed by high throughput sequencing (ChIP-Seq) of wild-type budding yeast cell chromatin. Remarkably, this PTM is observed not only at origins of DNA replication, but is also uniquely distributed on the promoters of highly transcribed RNA polymerase I, II and IIIregulated genes dedicated to protein synthesis and glycolysis. This includes the promoters of ribosomal protein (RP), tRNA, rRNA, and amino acid biosynthesis genes. Here we show that H3T45 phosphorylation, mediated by Cdc7-Dbf4, is required for polymerase recruitment and full expression of RP and tRNA genes. Moreover, this PTM is involved in the proper assembly of the replication machinery at origins of replication. Collectively, we identified an unexpected gene regulatory function for the DNA-replication kinase Cdc7-Dbf4 and identified a novel histone modification regulating the protein biosynthesis gene machinery and DNA replication in Saccharomyces cerevisiae.

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