Disordered transcription: Deciphering disordered transcription factors one-by-one with single-molecule techniques

BMC Seminar Thursday 25th of November, 12:00 on Zoom.

Speaker: Pétur Orri Heiðarsson, Associate Professor, Department of Biochemistry, University of Iceland

Title: Disordered transcription: Deciphering disordered transcription factors one-by-one with single-molecule techniques

Abstract: Most transcription factors in the human proteome consist of structured DNA-binding domains flanked by long intrinsically disordered activation domains and linker regions. Disordered regions are frequently involved in protein/DNA interactions and the activation domains often recruit components necessary for transcription. Disorder-to-order transitions are a common interaction-mode for disordered regions but they can also retain a degree of disorder after binding (termed fuzzy complex) or even remain fully disordered.

The extensive disorder of transcription factors places them at the edge of what current structural biology techniques can do and understanding their functions therefore requires a different approach. Single-molecule spectroscopy offers a powerful toolbox to monitor complex molecular systems and measure their conformational distributions and interaction patterns. These methods enable quantitative modelling of distances and dynamics in biomolecules on timescales spanning over 15 orders of magnitude.

I will illustrate how we can use single-molecule spectroscopy to study transcription factors and their interactions with chromatin, and then discuss what we have recently learned about the elusive neuronal reprogramming factor Ascl1.