Physical Interaction of Human Yin Yang 1 Protein with DNA.

Yin Yang 1 (YY1)'s interaction with DNA can result in various, even contradicting, effects on transcription in the form of initiation, activation, or repression. This surprising activity can be explained in the context of the YY1-DNA's complex structure. YY1's DNA-binding domain is formed by four zinc finger motifs. However, the sequence of both the zinc fingers and the linkers is non-canonical, which impairs their docking to the DNA duplex. Short linkers between the zinc fingers impose a concerted binding mechanism. Analysis of the sequences known to be recognized by YY1 suggests different contributions of particular zinc fingers in specific recognition of activated versus repressed promoters. Thermodynamic and kinetic studies show that, although the YY1's N-terminal fragment does not itself bind to DNA, it might regulate the interaction because its presence influences the binding parameters. Meta-analysis of YY1-DNA binding allowed us to observe that YY1's avidity to multiple binding sites is crucial in providing high-affinity specific sequence recognition. Alternatively, other trans-acting factors can modulate the YY1-DNA interaction and influence its outcome. This complex mechanism causes great sensitivity for individual point mutations, an increasing number of which are found in YY1 in cancer tissues.