Zinc Ions Modulate YY1 Activity: Relevance in Carcinogenesis

SIMPLE SUMMARY: YY1 is a protein regulator of gene expression that has been shown to be involved in the progression of numerous cancers. We recently described a previously unrecognized effect of zinc ions on YY1’s structure and activity. The cellular zinc level is tightly regulated, but at the same time, it differs in normal and malignant cells, providing a context that could explain YY1 dysfunction. This review explores possible mechanisms through which YY1’s interaction with zinc ions might affect its activity, resulting in abnormal gene expression pattern. ABSTRACT: YY1 is widely recognized as an intrinsically disordered transcription factor that plays a role in development of many cancers. In most cases, its overexpression is correlated with tumor progression and unfavorable patient outcomes. Our latest research focusing on the role of zinc ions in modulating YY1’s interaction with DNA demonstrated that zinc enhances the protein’s multimeric state and affinity to its operator. In light of these findings, changes in protein concentration appear to be just one element relevant to modulating YY1-dependent processes. Thus, alterations in zinc ion concentration can directly and specifically impact the regulation of gene expression by YY1, in line with reports indicating a correlation between zinc ion levels and advancement of certain tumors. This review concentrates on other potential consequences of YY1 interaction with zinc ions that may act by altering charge distribution, conformational state distribution, or oligomerization to influence its interactions with molecular partners that can disrupt gene expression patterns.