Yin Yang1 (YY1) is a ubiquitous expressed transcription factor that modulates a variety of biologic processes with prominent roles in cellular differentiation and tissue development. Recent advances in molecular biology, mouse genetics, and particularly high-throughput sequencing have greatly enhanced our understanding of YY1 functions and underlying mechanisms in regulating transcription and epigenetics. In this review, we summarize findings on the roles of YY1 in cell differentiation and tissue development, in particular in muscle, nerve, and immune cells/tissues.