Decoding chromatin organization in the nuclear environment.

Abstract

Chromatin structure tightly controls genome function within the nucleus. The nuclear environment is complex, featuring tension exerted by various force-generating proteins and molecular crowding modulated by different ionic concentrations. Disentangling these factors to understand how they affect chromatin structure would reveal the mechanism underlying the accessibility and organization of chromatin with an important connection to transcriptional activity and epigenetic regulation of genes. Nevertheless, it is unclear how chromatin adapts its structure to different nuclear environments. Here, we computationally characterize chromatin structures under tension, crowding, and ionic environments using a near-atomistic resolution chromatin model. Our simulations show that DNA unwrapping causes chromatin to break into a series of trimeric and tetrameric nucleosome clutches under tension. This irregularity further facilitates the formation of interdigitated chromatin structures via the trans interactions among multiple chains under a crowded environment, such as interphase heterochromatin and mitotic chromatin. Finally, our simulation shows that monovalent and divalent ions can further modulate chromatin structures, consistent with experiments. Since the nucleus features various environments at different cell cycle stages, our collective work can facilitate understanding the package of genetic materials in various cellular contexts and the genomic adaptation to an ever-changing external environment.