Role of H3K4 monomethylation in gene regulation

• Published in: Current opinion in genetics & development 2024-02, Vol.84, p.102153-102153, Article 102153
• Main Authors: Wang, Zhaoning, Ren, Bing
• Format: Article
• Language: English
• ISSN: 0959-437X; 1879-0380
• DOI: 10.1016/j.gde.2024.102153

Methylation of histone H3 on the lysine-4 residue (H3K4me) is found throughout the eukaryotic domain, and its initial discovery as a conserved epigenetic mark of active transcription from yeast to mammalian cells has contributed to the histone code hypothesis. However, recent studies have raised questions on whether the different forms of H3K4me play a direct role in gene regulation or are simply by-products of the transcription process. Here, we review the often-conflicting experimental evidence, focusing on the monomethylation of lysine 4 on histone H3 that has been linked to the transcriptional state of enhancers in metazoans. We suggest that this epigenetic mark acts in a context-dependent manner to directly facilitate the transcriptional output of the genome and the establishment of cellular identity. •H3K4 monomethylation (H3K4me1) is a conserved histone mark.•H3K4me1 is implicated in various regulatory stages of gene regulation.•Data supporting and opposing a direct role of H3K4me1 in gene regulation are reviewed.•We propose a new conceptual framework to reconcile these experimental observations.