Jan-Hendrik Spille
A single molecule view of structure and dynamics in transcription condensates
Abstract:
A phase separation model has been proposed to explain the accumulation of transcription regulators in at highly active chromatin elements. We use single molecule imaging to investigate how constituent proteins interact with endogenous transcription condensates. We find that RNA Pol II and other proteins are enriched in condensates due to DNA binding rather than weak, multivalent interactions of their intrinsically disordered regions (IDRs). IDRs facilitate recruitment but, by themselves, partition only weakly into condensates. The Pol II CTD is not sufficient but required for recruitment to condensates. Multicolor dSTORM imaging of post-translational histone modifications elucidates the chromatin context of transcription condensates. Core enrichment of H3K4me3 promoter marks in several distinct foci per condensates suggests colocalization of multiple transcribed elements in transcription hubs. Enhancers localize more peripheral in a layered chromatin structure. In ongoing work, we uncover how IDRs position transcription factors within this chromatin landscape. Our findings shed new light on mechanisms of transcription spatial organization in the cellular environment and emphasize the value of in situ single molecule studies.
Speaker: Jan-Hendrik Spille, University of Illinois Chicago
Dr. Spille is an Assistant Professor at the University of Illinois Chicago working in experimental biophysics. He completed his undergraduate studies in Physics at the University of Wuerzburg (2009) and his doctorate at the University of Bonn in Germany (2014) with a thesis on 3D single particle tracking. From 2015 – 2019, Dr. Spille was a postdoctoral fellow with Ibrahim Cisse at MIT before starting his independent group in Chicago. He uses single molecule imaging to study chromatin organization and the role of biomolecular condensates in transcription regulation. His work is supported by the NSF, the NIH, and RCSA Scialog awards.
Seminars start at 4:00 pm, and refreshments will be served at 3:45 pm. All seminars are held in the 2136 Physical Sciences Complex (#415) unless otherwise noted.