Condensed but liquid-like domain organization of active chromatin regions in living human cells
Tadasu Nozaki*, Soya Shinkai*, Satoru Ide*, Koichi Higashi*, Sachiko Tamura, Masa A. Shimazoe, Masaki Nakagawa, Yutaka Suzuki, Yasushi Okada, Masaki Sasai, Shuichi Onami, Ken Kurokawa, Shiori Iida, Kazuhiro Maeshima *co-first authors
Science Advances (2023) 9, eadf1488 DOI:10.1126/sciadv.adf1488
The human genome chromatin can be classified into euchromatin and heterochromatin, which have high and low transcription activities, respectively. In the classical view, it was believed that euchromatin has an open and decondensed structure, while heterochromatin is highly condensed.
A research team led by Professor Kazuhiro Maeshima of Genome Dynamics Laboratory (NIG), including a graduate student (currently a Research Associate at Harvard Univ.) Tadasu Nozaki, Assistant Professor Satoru Ide, Technical Stuff Sachiko Tamura, SOKENDAI graduate student Masa A. Shimazoe, SOKENDAI graduate student (JSPS Research Fellow DC2) Shiori Iida, together with Assistant Professor Koichi Higashi and Professor Ken Kurokawa of Genome Evolution Laboratory (NIG), and Senior Research Scientist Soya Shinkai and Team Leader Shuichi Onami of RIKEN BDR, have found euchromatin forms condensed chromatin domains. This finding suggests an innovative model that condensed structure is the default state of chromatin.
In this work, motions of fluorescently labeled nucleosomes in euchromatin in living human cells were investigated with a super-resolution microscope. Two neighboring nucleosomes were observed simultaneously with different colored fluorescent dyes. The research team discovered that movements of nucleosome pairs within 150 nm in the distance were correlated. This shows that euchromatin forms irregularly condensed chromatin domains with ~150 nm diameters. Further analysis revealed that nucleosomes within a domain behave like a liquid. On the other hand, euchromatin is stable at the chromosome scale, and exhibits a solid-like behavior.
This liquid-like behavior of nucleosomes can facilitate transcription, DNA replication, and repair in condensed domains. Also, the condensed domains can protect DNA from radiation damage. Solid-like behavior of chromatin at the chromosome scale can contribute to maintaining the genome by preventing entanglements or breaks of long chromatin. Chromatin is locally dynamic and reactive, and globally stable.
This work was supported by JSPS Fellowship, JSPD grants (21H02453, 22H05606, 21H02535, 20H05550, 20H05936, 16H06279(PAGS), 22H04925 (PAGS)), a Japan Science and Technology Agency CREST grant (JPMJCR15G2), JST SPRING(JPMJSP2104), and the Uehara Memorial Foundation.
Figure: Nucleosomes form irregularly condensed chromatin domains by their intrinsic sticky nature (blue clusters in the balloon). Nucleosomes show dynamic liquid-like behavior inside a domain, which promotes DNA transactions. On the other hand, the solid-like behavior of chromatin on the chromosome scale helps to maintain the genome by preventing entanglements or breaks of long chromatin.
Video of nucleosome pairs at euchromatin labeled by two different fluorescent dyes and recorded simultaneously. The upper row shows a neighboring nucleosome pair with correlated movements. The lower row depicts a distant nucleosome pair with uncorrelated movements.