Xue Mande, Ma Lijun, Li Xiaoyi, Zhang Huairen, Zhao Fengyue, Liu Qian, Jiang Danhua
State Key Laboratory of Seed Innovation, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
Nat Commun. 2025 May 13;16(1):4408. doi: 10.1038/s41467-025-59711-4.
Although histone modifications are linked with chromatin activities such as transcription, proofs of their causal importance remain limited. Sequence variants within each histone family expand chromatin diversity and may carry specific modifications, further raising questions about their coordination. Here, we investigate the role of lysine 4 (K4) in two Arabidopsis H3 variants, H3.1 and H3.3. K4 is essential for H3.3 function but not H3.1 in plant development. Mutating K4 in H3.3 drastically reduced H3K4 methylation levels and mimicked the transcriptomic effects of losing SDG2, the major H3K4 trimethylation (H3K4me3) methyltransferase. Moreover, H3.3K4 and SDG2 are required for de novo gene activation and RNA Pol II elongation. H3K4 methylation is preferentially enriched on H3.3, likely due to the coordinated activity of H3.3 deposition and H3K4 methylation. Furthermore, we reveal the diverse impacts of K4 nearby residue mutations on H3K4 methylation and H3.3 function. These findings highlight H3.3 as a critical substrate for H3K4 methylation, which is important for gene expression regulation.
尽管组蛋白修饰与染色质活性（如转录）相关联，但其因果重要性的证据仍然有限。每个组蛋白家族内的序列变异扩展了染色质的多样性，并可能携带特定的修饰，这进一步引发了关于它们如何协调的问题。在这里，我们研究了赖氨酸4（K4）在两种拟南芥H3变体H3.1和H3.3中的作用。在植物发育过程中，K4对H3.3的功能至关重要，但对H3.1并非如此。在H3.3中突变K4会大幅降低H3K4甲基化水平，并模拟失去主要的H3K4三甲基化（H3K4me3）甲基转移酶SDG2后的转录组效应。此外，H3.3K4和SDG2是从头基因激活和RNA聚合酶II延伸所必需的。H3K4甲基化优先富集在H3.3上，这可能是由于H3.3沉积和H3K4甲基化的协同作用。此外，我们揭示了K4附近残基突变对H3K4甲基化和H3.3功能的不同影响。这些发现突出了H3.3作为H3K4甲基化的关键底物，这对基因表达调控很重要。
