Mechanisms of Yin Yang 1 in Oncogenesis: the Importance of Indirect Effects

Yin Yang 1 (YY1) is a ubiquitously expressed transcription factor that performs numerous functions including transcriptional regulation, cell growth control, apoptosis, large-scale chromosomal dynamics, and X-chromosome inactivation. YY1 clearly is able to control cell functions, including proliferation, by acting as a transcription factor either to activate or repress specific genes. Based on its ability to regulate cell growth control genes, it has been argued that YY1 can function as an oncogene that initiates oncogenesis. Although this is an attractive hypothesis, no reports indicate that YY1 can acutely transform cells in culture or form tumors within animals when overexpressed. Thus, it remains unclear whether YY1 is a "classic" oncogene. However, YY1 controls many diverse cell functions, and these functions may provide clues to its role in oncogenesis. We propose that in many cases YY1 may function in oncogenesis and disease progression through "indirect" effects by virtue of its role in either recruiting Polycomb group proteins to DNA, regulating mutator protein accumulation, controlling large-scale chromosomal dynamics or genomic integrity. Disruption of these functions may causally initiate cancer or may contribute to disease progression. Targeting YY1 functions provides possible avenues for clinical intervention.