A mitogen‐ and anisomycin‐stimulated kinase phosphorylates HMG‐14 in its basic amino‐terminal domain in vivo and on isolated mononucleosomes.

The rapid, transient induction of 80‐100 immediate‐early (IE) genes upon mitogenic stimulation occurs irrespective of protein synthesis and is mediated by modification of existing proteins. Two mechanisms, not mutually exclusive, involving modification either of sequence‐specific transcription factors or of structural chromatin proteins primed by pre‐association with responsive effectors are conceivable. Here, we show that upon IE gene induction, the non‐histone high‐mobility‐group protein HMG‐14, but not the related protein HMG‐17, becomes serine phosphorylated in its basic, amino‐terminal region close to where it binds nucleosomal DNA. Phosphorylation, normally transient, occurs independent of transcription and is quantitative and prolonged during superinduction. Brief micrococcal nuclease digestion substantially releases HMG‐14 from nuclei in the mononucleosome‐bound state. Finally, mononucleosomes prepared from mitogen‐stimulated, but not control, cells contain a mitogen‐activated kinase that phosphorylates HMG‐14 in vitro on the same site(s) as in intact cells. The association of HMG‐14 and its mitogen‐activated kinase with nuclease‐sensitive mononucleosomes has implications for models of mitogen‐stimulated IE gene induction.