Nutritional stress signaling in budding yeast includes phosphorylation of histone H3T11 (H3pT11).
To understand upsteam signaling of H3pT11, we dissected kinases involved in this process. We found that H3pT11 requires both AMPK and CK2 kinases. However, these kinase do not directly phosphorylate H3T11 but instead directly phosphorylate the Tda1 kinase. Tda1 is a yeast AMPK interacting kinase that phosphorylates H3T11 in vitro and in vivo. Phosphorylation of Tda1 is required for its proper histone kinase activity and its protein stability. The Tda1 kinase thus integrates signals of multiple upstream kinases to regulate H3T11 phosphorylation upon nutrient stress.