UC San Diego

Post-translational histone modifications have a critical role in regulating transcription, the cell cycle, and stress responses. These histone modifications can occur in complex patterns depending on the activity of multiple chromatin modifiers. Histone acetyltransferases (HAT) are one of the classes of chromatin modifiers important for altering chromatin structure and activating transcription. Gcn5 is a highly conserved catalytic subunit found in multiple HAT complexes that regulate gene expression. In addition to HAT activity, phosphorylation of histones and non-histone proteins by protein kinases is also important. Kinases are necessary for signaling pathways such as a rapid response to stress. Here we define previously unsuspected interactions between Gcn5 and different isoforms of the protein kinase CK2, in Saccharomyces cerevisiae. We show that although CK2 has hundreds of targets in vivo, distinctions can be made between the individual catalytic subunits encoded by CKA1 and CKA2. This distinction was found in cells lacking Gcn5. Loss of CKA1 and CKA2 suppresses gcn5∆ mutant sensitivity to elevated temperatures and DNA damage induced by hydroxyurea, respectively. Suppression is lost when either CKB1 or CKB2 are also deleted. Loss of CKA1, but not CKA2 partially recovers the decrease in H3K9,K14ac in gcn5∆ cells. A directed screen of tyrosine residues of core histones demonstrated novel roles of multiple residues, but left unanswered key questions into the interactions seen between Gcn5 and CK2. Together, this work has shown distinct functions of the CK2 isoforms in their roles in specific stress responses and interactions with Gcn5.