Nucleosome condensate and linker DNA alter chromatin folding pathways and rates.

Abstract

Atomic structures of chromatin have become increasingly accessible, largely through cryo-EM techniques. Nonetheless, these approaches often face limitations in addressing how intrinsic in vivo factors influence chromatin organization. We present a structural characterization of chromatin under the combined effects of nucleosome condensate crowding and linker DNA length variation-two critical in vivo features that have remained challenging to capture experimentally. This work leverages a novel application of non-Markovian dynamical modeling, providing accurate mapping of chromatin folding kinetics and pathways. Our findings support a hypothesis that in vivo chromatin organization arises from folding intermediates advancing toward a stable fibril configuration, potentially resolving longstanding questions surrounding chromatin atomic structure.