Replication-dependent histone labeling dissects the physical properties of euchromatin/heterochromatin in living human cells

• DOI: 10.1126/sciadv.adu8400
• Publication Date: 2025-03-28T18:05:49Z
• Authors: Katsuhiko Minami; Kako Nakazato; Satoru Ide; Kazunari Kaizu; Koichi Higashi; Sachiko Tamura; Atsushi Toyoda; Koichi Takahashi; Ken Kurokawa; Kazuhiro Maeshima
• Keywords: Euchromatin; Replication timing; Heterochromatin protein 1; Constitutive heterochromatin

A string of nucleosomes, where genomic DNA is wrapped around histones, organized in the cell as chromatin, ranging from euchromatin to heterochromatin, with distinct genome functions. Understanding physical differences between and heterochromatin crucial, yet specific labeling methods living cells remain limited. Here, we have developed replication-dependent histone (Repli-Histo) mark nucleosomes based on replication timing. Using this approach, investigated local nucleosome motion four known chromatin classes, human mouse cells. The more euchromatic (earlier-replicated) heterochromatic (later-replicated) regions exhibit greater lesser motions, respectively. Notably, profile each class persists throughout interphase. Genome essentially replicated although timing perturbed. Our findings, combined computational modeling, suggest that earlier-replicated accessibility, can be a major determinant genome-wide