物理的性質から考えるクロマチンやDNAのアクセシビリティ

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2025-06-18 国立遺伝学研究所

国立遺伝学研究所・前島研究室は、ヒト細胞内のクロマチン構造が遺伝子転写やDNA複製に与える影響を「物理的性質」と「アクセシビリティ」の視点から解明しました。ユークロマチンは「液体様」に、ヘテロクロマチンは「ゲル様」に振る舞い、これは転写因子などの大きな分子が内部へアクセスできる度合いに直結します。この性質は、DNA上の遺伝情報がどの程度利用されるかに深く関与し、ゲノム機能の制御に影響します。論文はJournal of Molecular Biology誌の特集号に掲載されました。

物理的性質から考えるクロマチンやDNAのアクセシビリティ図:ユークロマチン・ヘテロクロマチンの物理的性質とアクセシビリティ
生きた細胞内で、遺伝子の転写が活発に行われるユークロマチン領域(IA, IB)はより「液体様」に、転写の抑制されたヘテロクロマチン(II, III)はより「ゲル様」に振る舞う。この性質は、転写因子(紫)などが短い時間にどれほどクロマチン内部へ「アクセス」しやすいかと直結している。

<関連情報>

ユークロマチンとヘテロクロマチン:DNAのアクセシビリティと転写への影響 Euchromatin and Heterochromatin: Implications for DNA Accessibility and Transcription

Katsuhiko Minami, Adilgazy Semeigazin, Kako Nakazato, Kazuhiro Maeshima
Journal of Molecular Biology  Available online: 6 June 2025
DOI:https://doi.org/10.1016/j.jmb.2025.169270

Highlights

  • Repli-Histo labeling marks euchromatin and heterochromatin in living cells.
  • Euchromatic nucleosomes fluctuate like a liquid; heterochromatin behaves like a gel.
  • Local nucleosome fluctuation facilitates protein access into chromatin domains.
  • Heterochromatin shows moderate DNA accessibility on a longer time scale.
  • DNA accessibility depends on both structure and time-scale-dependent dynamics.

Abstract

The organization and dynamics of chromatin play a fundamental role in transcriptional regulation. In higher eukaryotic cells, genomic DNA is wrapped around histones to form nucleosomes, which are irregularly folded into condensed chromatin domains ranging from euchromatin to heterochromatin. These domains have distinct functions and physical differences that impact chromatin accessibility. Recently, replication-dependent histone (Repli-Histo) labeling was developed to specifically mark nucleosomes in euchromatin and heterochromatin based on DNA replication timing. Using this technique, nucleosome behavior was revealed across four chromatin classes, from euchromatin to heterochromatin. Interestingly, nucleosome motion is progressively constrained along this spectrum. Nucleosomes in euchromatin domains fluctuate more like a liquid, whereas those in heterochromatin are highly constrained, resembling a gel-like state. How these physical properties relate to DNA/chromatin accessibility and genome function remains an important question. In this review, we discuss not only the physical differences between euchromatin and heterochromatin but also how nucleosome behavior influences the physical access of proteins to their DNA targets within chromatin, which underlies the initiation of essential DNA transaction processes, including transcription.

生物環境工学
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