Interphase chromatin undergoes a local sol-gel transition upon cell differentiation.

Abstract

Cell differentiation, the process by which stem cells become specialized, is associated with chromatin reorganization inside the cell nucleus. Here, we measure the chromatin distribution and dynamics in embryonic stem cells in vivo before and after differentiation into neurons. We find that undifferentiated chromatin is less compact, more homogeneous and more dynamic than differentiated chromatin. Further, we present a noninvasive experimental strategy that uses intrinsic chromatin dynamics, to measure chromatin rheology across a large range of timescales, and elucidates the viscoelastic nature of chromatin in live cells. Moreover, by spatially resolving the dynamics in different regions of the cell nucleus, our method reveals local rheology of the chromatin polymer in both euchromatin and heterochromatin states. The measured rheology reveals that undifferentiated chromatin behaves like a Maxwell fluid, while differentiated chromatin shows a coexistence of fluid-like (sol) and solid-like (gel) phases. Our data suggest that chromatin undergoes a local sol-gel transition upon cell differentiation, corresponding to the formation of the more dense and transcriptionally inactive heterochromatin [1]. This work was supported by the National Institutes of Health Grant R00-GM104152, the National Science Foundation (NSF) Grants CAREER PHY-1554880 and CMMI-1762506, New York University (NYU) MRSEC NSF Grant DMR-1420073 and NYU Whitehead Fellowship for Junior Faculty in Biomedical and Biological Sciences (to AZ). Eshghi I, Eaton JA and Zidovska A. Phys. Rev. Lett., 126, 228101 (2021).