Yanhui Xu - Structural Insights into Transcription Initiation

Professor Xu talked about efforts on mammalian transcriptional initiation mechanisms. The structures of the transcription pre-initiation complex (PIC), including TFIID, were determined by cryo-EM. The structures revealed the recognition of various types of promoters and the assembly process of complete PIC and proved the role of Mediator in PIC assembly and CTD phosphorylation. Transcription initiation process was visualized by structures of 16 de novo transcribing complexes, showing molecular mechanism of a transition from initially transcribing complex (ITC) to early elongation complex (EEC) accompanying considerable conformational changes. In addition, the mechanism of PIC assembly on chromatin was also studied. Direct interactions between the transcription initiation complex and the +1 nucleosome were found for the first time, indicating that the +1 nucleosome plays an important regulatory role in PIC-Mediator assembly on chromatin. This study established a direct correlation between epigenetic and transcription initiation. The above series of studies provided a framework for the subsequent study of gene expression regulation.