Biochemistry Seminars

Throughout the academic year, the Department of Biochemistry invites professors from other universities and institutes to speak at the University of Colorado Boulder. These seminars provide an opportunity for faculty and students to learn about exciting current research at other universities.

Kazuhiro MaeshimaDr. Kazuhiro Maeshima
Friday, February 28 | 1:30 pm | JSCBB B231 
Talk Title: Single nucleosome imaging reveals that active RNA polymerase II globally constrains genome chromatin
Host: Dr. Karolin Luger 

Eukaryotic chromatin is a negatively charged polymer consisting of genomic DNA, histones, and various non-histone proteins. Over the last ten years, newly developed technologies have drastically shifted our view on chromatin from a static regular structure to a more irregular and dynamic one, locally like a fluid (1). It has been assumed that chromatin organization and dynamics play a critical role in gene transcription. However, how they interplay remains unclear. To approach this issue, the single-nucleosome imaging is a powerful technique because local chromatin motion reflects chromatin organization in living cells (2). Using the imaging technique, we investigated genome-wide chromatin behavior under various transcriptional conditions in living human cells (3). While transcription by RNA polymerase II (RNAPII) is generally thought to need more open and dynamic chromatin, surprisingly, we found that active RNAPII globally constrains chromatin movements. RNAPII inhibition or RNAPII rapid depletion released the chromatin constraints and increased chromatin motion. On the other hand, treatment of RNA polymerase I inhibitor or splicing inhibitor did not have significant effect on the chromatin motion. Furthermore, chromatin mobility also increased in quiescent G0 cells and UV-irradiated cells, which are transcriptionally less active. Our results demonstrated that chromatin is globally constrained by loose connections through active RNAPII (3), which is compatible with models of the classical transcription factories or the recently reported liquid droplet formation of transcription-related factors. Together with our computational modeling, we propose the existence of loose chromatin networks via transcription machinery, presumably for efficient gene transcription.

Eva NogalesDr. Eva Nogales
Wednesday, March 4 | 3:30 – 4:30pm | JSCBB A115 - Butcher Auditorium
Talk Title: Challenging Protein Complexes that Regulate the Expression of our Genes: Visualizing themin Action using Cryo-EM
                 Host: Biophysics Students 

Because only small amounts of sample areneeded, and due to its potential to deal with compositional and conformational mixtures,cryo-electron microscopy (cryo-EM) is capable of studying challenging systemsthat otherwise defy structural characterization. These challenging systemsinclude the incredibly flexible human TFIID complex, essential for corepromoter recognition and assembly of the Pol II transcription pre-initiationcomplex, and the delicate humanpolycomb repressive complex 2 (PRC2) involved in gene silencing.

TFIID functions as a central hub in therecognition of the core promoter sequences and neighboring chromatin marks andloads the TATA-box binding protein (TBP) onto the DNA. Ourstudies have shown that TFIID undergo dramatic conformational transitions thatare linked to its binding to DNA. While dealing with the complexity of TFIID’sconformational landscape has been challenging, our studies have now led to afull description of the subunit architecture of TFIID and to a model of how thestructure and dynamics of the complex are used to load TBP onto DNA only whenthe core promoter is recognized, leading to the proper recruitment of Pol II atthe transcription start site.

PRC2 methylateslysine 27 of histone H3 and is essential for cellular differentiation anddevelopment. Our structure of human PRC2 in complex with JARID2 and AEBP2showed how AEBP2 stabilizes the full complex, and how the two cofactors mimicthe binding of histone H3 tails. We also described the interaction of PRC2 witha dinucleosome, showing the double engagement of consecutive nucleosomes by thecomplex for different linker lengths. Our recent analysis using differentpost-transcriptional modifications in substrate nucleosomes point to aninteresting interplay between different histone modifications and cofactors inthe regulation of PRC2 enzymatic activity.


biochemistry logoUndergraduate Research Symposium​
Wednesday, March 11 | 3:30 – 4:30pm | JSCBB A115 - Butcher Auditorium
Host: Dr. Jeffrey Cameron