Distinct Histone H3 Lysine 27 Modifications Dictate Different Outcomes of Gene Transcription

• Published in: Journal of molecular biology Vol. 436; no. 7; p. 168376
• Main Authors: Konuma, Tsuyoshi, Zhou, Ming-Ming
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.04.2024
• Subjects: Acetylation; chromatin; Chromatin - genetics; Chromatin - metabolism; chromatin biology; gene transcription; genes; histone code; histone modifications; histones; Histones - genetics; Histones - metabolism; lysine; Lysine - genetics; Lysine - metabolism; methylation; molecular biology; Protein Domains; transcription (genetics); Transcription, Genetic; Transcriptional Activation; chromatin biology; gene transcription; histone modifications
• ISSN: 0022-2836; 1089-8638; 1089-8638
• DOI: 10.1016/j.jmb.2023.168376

A three-phase traffic light system model showing that histone H3K27me3 marks for transcriptional silencing, H3K27cr for transcriptional repression, and H3K27ac for transcriptional activation, respectively. [Display omitted] •Site-specific histone modifications direct gene transcription in chromatin.•Different histone modifications influence gene transcription outcomes.•Histone H3 lysine 27 (H3K27) acetylation (Kac), trimethylation (Kme3), and crotonylation (Kcr), dictate gene transcriptional activation, silence, and repression in chromatin, respectively.•H3K27ac/me3/cr-directed gene transcription represents as a long-awaited verification of the “Histone code hypothesis”. Site-specific histone modifications have long been recognized to play an important role in directing gene transcription in chromatin in biology of health and disease. However, concrete illustration of how different histone modifications in a site-specific manner dictate gene transcription outcomes, as postulated in the influential “Histone code hypothesis”, introduced by Allis and colleagues in 2000, has been lacking. In this review, we summarize our latest understanding of the dynamic regulation of gene transcriptional activation, silence, and repression in chromatin that is directed distinctively by histone H3 lysine 27 acetylation, methylation, and crotonylation, respectively. This represents a special example of a long-anticipated verification of the “Histone code hypothesis.”