How does RNA polymerase II cooperate with initiation factors to locate transcription start sites throughout the genome? A new cross-linking approach reveals previously unknown initiation factor–binding sites on the polymerase surface. The resulting model of the transcription initiation complex suggests that initiation factors cooperate above and inside the polymerase active center cleft to open DNA and find the transcription start site. In all living cells, the expression of genetic programs is governed by the dynamic transcriptome, which is established mainly by regulated transcription initiation at gene promoters. Thus, if we want to understand gene regulation, we must know the mechanism of transcription initiation. Initiation by RNA polymerase II (Pol II), which catalyzes eukaryotic messenger RNA transcription, requires the general transcription factors TFIIB, TFIID (containing the TATA box–binding protein, TBP), TFIIE, TFIIF and TFIIH, which assemble with the polymerase into a preinitiation complex (PIC) at the promoter1–4. The structure of the large and complex PIC remains under debate even at a topological level5. On page 696 of this issue, new work from Chen et al. of the Hahn laboratory6 provides insights into the PIC architecture and demonstrates an approach for elucidating the topology of a transient multicomponent complex even when only partial structural information is available.