Three-dimensional multiphase liquid chromatin model of eukaryotic nucleus
ORAL
Abstract
The interior of the eukaryotic cell nucleus has a crowded and heterogeneous environment packed with chromatin polymers, regulatory proteins, and RNA molecules. Chromatin polymer, assisted by epigenetic modifications, protein and RNA binders, forms multi-scale compartments which help regulate genes in response to cellular signals. Furthermore, chromatin compartments are dynamic and tend to evolve in size and composition in ways that are not fully understood. To understand and disentangle the complex interplay of forces that contribute to the emergent patterns of chromatin organization and dynamics, we have devised a phenomenological field-theoretic model of the nucleus as a multiphase condensate of liquid chromatin types. Armed with the developed 3D mesoscopic model of nuclear chromatin, we have shed light on the distinct dynamical and structural contributions of chromatin-type interactions, the intermingling of chromosomal territories, and lamina binding. We also shed light on the dynamical heterogeneity and coherent motions of chromatin domains which are fully captured by an interplay of micro-phase separation of chromatin types and lamina binding.
–
Publication: [1] A liquid state perspective on dynamics of chromatin compartments, R. Laghmach, M. Di Pierro and D. A. Potoyan, Frontiers in Molecular Biosciences 8 :781981 (2022) https://doi.org/10.3389/fmolb.2021.781981<br>[2] The interplay of chromatin phase separation and lamina interactions in nuclear organization, R. Laghmach, M. Di Pierro and D. A. Potoyan, Biophysical Journal (2021) https://doi.org/10.1016/j.bpj.2021.10.012<br>[3] Mesoscale liquid model of chromatin recapitulates nuclear order of eukaryotes, R. Laghmach, M. Di Pierro and D. A. Potoyan, Biophysical Journal, 0006-3495 (2020) https://doi.org/10.1016/j.bpj.2019.09.013