Super-resolution imaging of chromatin structure and dynamics

Melikel Lakadamyal (Penn Med, Philadelphia)

Mar 16. 2020, 14:30 -- 15:10

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 estimate 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-tyoe specific and correlates with the level of cell pluripotency. Using single molecule tracking of nucleosomes and transcription factors, we further reveal a heterogenous landscape of chromatin dynamics that differentially maps onto transcription factor dynamics depending on transcription factor's ability to bind nnucleosome's. Overall, our results are revealing new insights into the intimate link between chromatin structure, dynamics and gene activity.

Further Information
ESI Boltzmann Lecture Hall
Associated Event:
Chromatin Modeling: Integrating Mathematics, Physics, and Computation for Advances in Biology and Medicine (Thematic Programme)
Christos Likos (U Vienna)
Stephanie Portillo (NYU, New York)
Tamar Schlick (NYU, New York)