Biophysics Seminar: Melike Lakadamyali, UPENN: Super-resolution imaging of chromatin structure and dynamics|Joseph Henry Room

Mon, Nov 25, 2019, 12:00 pm
A free lecture open to the public.

Nucleosomes help structure chromosomes by compacting DNA into fibers. Chromatin organization plays an important role for regulating gene expression; however, due to the highly crowded nuclear environment and the nanometer length scales of chromatin fibers, it has been very difficult to visualize chromatin in vivo. We have overcome this challenge by developing highly quantitative and multiplexed super-resolution microscopy methods that allow us to not only visualize chromatin with nanoscale spatial and kilobase genomic resolution but also allow us to count the number of nucleosomes along the chromatin fiber. Our results reveal a new paradigm of chromatin compaction in the form of heterogeneous groups of nucleosomes, which we termed nucleosome clutches, in analogy to egg clutches. We have further shown that the nanoscale chromatin organization is highly cell-type specific and correlates with the level of cell pluripotency. Using single molecule tracking, we have also uncovered a heterogeneous chromatin mobility landscape that is both cell-type specific and that functionally maps to the mobility of canonical as well as pioneer transcription factors. Overall, our results are revealing new insights into the intimate link between chromatin structure, dynamics and gene activity.