Regulation of Yin Yang 1 by Tyrosine Phosphorylation [Signal Transduction]

July 21st, 2015 by Wang, G. Z., Goff, S. P.

Yin Yang 1 (YY1) is a member of the GLI-Kruppel class of DNA and RNA binding transcription factors that can either activate or repress gene expression during cell growth, differentiation and embryogenesis. While much is known about YY1 interacting proteins and the target promoters regulated by YY1, much less is known about YY1 regulation through post-translational modifications. In this study, we show that YY1 is tyrosine phosphorylated in multiple cell types. Using a combination of pharmacological inhibition, kinase overexpression, and kinase knockout studies, we demonstrate that YY1 is a target of multiple Src family kinases in vitro and in vivo. Moreover, we have identified multiple sites of YY1 phosphorylation and analyzed the effect of phosphorylation on the activity of YY1-responsive retroviral and cellular promoters. Phosphorylation of tyrosine 383 interferes with DNA and RNA binding, leading to the downregulation of YY1 activity. Finally, we provide first evidence that YY1 is a downstream target of epidermal growth factor receptor (EGFR) signaling in vivo. Taken together, the identification of YY1 as a target of Src family kinases provide key insights into the inhibitory role of tyrosine kinases in modulating YY1 activity.