Mechanical Interplay of Chromatin and Liquid-Liquid Phase Separated Condensates

ORAL

Abstract

DNA is organized into chromatin, a complex material which stores information and controls gene expression. One mechanism for biological organization, particularly in the crowded nucleus, is liquid-liquid phase separation (LLPS). Here, we use two optogenetic technologies to show that liquid condensates displace chromatin as they grow. We also demonstrate that these synthetic condensates localize to regions of low-density chromatin. We develop a minimal physical model to explain this stiffness selectivity, wherein droplets prefer low-density chromatin regions due to a lower mechanical energy of deformation. By utilizing these spatiotemporally-controllable optogenetic systems, we construct a phase diagram of an intrinsically disordered transcriptional regulator and estimate the stiffness of the chromatin network. Our work thus not only sheds light on the role of LLPS in chromatin organization but also uses the physical principles of phase separation to elucidate mesoscale features of the nucleus.

*This work was supported in part by the National Science Foundation, through the Center for the Physics of Biological Function (PHY-1734030)
and the Graduate Research Fellowship Program (DCE-1656466, D.S.W.L.), and NIH Grants R01 GM082938, U01 DA040601, and the Howard Hughes Medical Institute.

–

Presenters

  • Daniel Lee

    • Princeton University
    • Lewis-Sigler Institute for Integrative Genomics, Princeton University

Authors

  • Daniel Lee

    • Princeton University
    • Lewis-Sigler Institute for Integrative Genomics, Princeton University

  • Yi-Che Chang

    • Department of Chemistry, Princeton University

  • Yongdae Shin

    • Department of Mechanical and Aerospace Engineering, Seoul National University

  • David Sanders

    • Department of Chemical and Biological Engineering, Princeton University

  • Dan Bracha

    • Department of Chemical and Biological Engineering, Princeton University

  • Pierre Ronceray

    • Princeton Center for Theoretical Science, Princeton University
    • Princeton University
    • Princeton Center for Theoretical Sciences, Princeton University

  • Ned Wingreen

    • Lewis-Sigler Institute for Integrative Genomics, Princeton University
    • Princeton University
    • Department of Molecular Biology, Princeton University
    • Department of Molecular Biology and Lewis-Sigler Institute for Integrative Genomics, Princeton University

  • Cliff Brangwynne

    • Princeton University
    • Howard Hughes Medical Institute