More About The Alexandros Pertsinidis Lab Minus iconIcon indicating subtraction, or that the element can be closed. Plus IconIcon indicating addition, or that the element can be opened. Arrow (down) icon.An arrow icon, usually indicating that the containing element can be opened and closed.

Transcription Initiation of Eukaryotic mRNA Coding Genes

The regulation of mRNA transcription plays a key role in relaying signals from the environment and during development into the gene expression program of a cell. During transcription initiation, a large, multi-molecular machinery assembles on the promoter of a gene, to enable proper positioning of the RNA Polymerase enzyme and commence accurate mRNA synthesis. The rate of initiation is further controlled by transcriptional activators that recognize cis-regulatory DNA elements, proximal and distant to promoters, to direct remodeling of the local chromatin state and recruitment of the core machinery, often through interactions mediated by separate, large co-activator complexes.

Tremendous amount of work has identified the key molecular players and has revealed high-resolution snapshots of many intermediates in this pathway, however a complete, detailed mechanistic understanding of activator-dependent transcription initiation is still lacking. We are focusing on dissecting the assembly pathway and the structural organization of the transcription pre-initiation complex (comprised of the general transcription factors TFIIA,TFIIB,TFIID,TFIIF,TFIIE,TFIIH and RNA Polymerase II), and how it is regulated by the action of transcription activators.

We are applying single-molecule detection techniques to overcome some of the challenges associated with traditional, ensemble biochemical methods and probe this complex, multi-step process. Our goal is to obtain a high-resolution structural view of transcription initiation, in real-time and ultimately as is occurs in the physiological context of the sub-nuclear chromatin organization.