Abstract
Ying–Yang 1 protein (YY1) supports specific, unidirectional
initiation of messenger RNA production by RNA polymerase II from two
adjacent start sites in the adeno-associated virus P5 promoter, a
process which is independent of the TATA box-binding protein (TBP). The
2.5-Å resolution YY1-initiator element cocrystal structure reveals
four zinc fingers recognizing a YY1-binding consensus sequence.
Upstream of the transcription start sites protein–DNA contacts involve
both strands and downstream they are virtually restricted to the
template strand, permitting access to the active center of RNA
polymerase II and ensuring specificity and directionality. The observed
pattern of protein–DNA contacts also explains YY1 binding to a
preformed transcription bubble, and YY1 binding to a DNA/RNA hybrid
analog of the P5 promoter region containing a nascent RNA transcript. A
model is proposed for YY1-directed, TBP-independent transcription
initiation.