美国西奈山伊坎医学院Ian Maze等研究人员合作发现，双向组蛋白单胺基化动态调节神经节律性。2025年1月8日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员表示，组蛋白H3在Gln5位点的单胺化是大脑中一种重要的表观遗传标记家族，在基因表达的许可性调节中具有关键作用。研究人员之前证明了，组蛋白H3的Gln5位点的血清素化和多巴胺化（分别为H3Q5ser和H3Q5dop）是由转谷氨酰胺酶2（TG2）催化的，并且能够改变局部和全局的染色质状态。

研究人员发现TG2还作为H3单胺化的擦除酶和交换酶，包括H3Q5组胺基化（H3Q5his）。该标记在大脑中具有昼夜节律性表达，并参与昼夜节律基因表达和行为。研究人员发现，与H3Q5ser不同，H3Q5his抑制了WDR5的结合。WDR5是组蛋白H3第4位赖氨酸（H3K4）甲基转移酶复合物的核心成员，从而拮抗了H3K4上的甲基转移酶活性。

综合这些数据，研究人员阐明了一种机制，即通过单一的染色质调控酶能够感知化学微环境，进而影响细胞的表观遗传状态，而这种动态变化在神经节律性的调控中具有关键作用。

附：英文原文

Title: Bidirectional histone monoaminylation dynamics regulate neural rhythmicity

Author: Zheng, Qingfei, Weekley, Benjamin H., Vinson, David A., Zhao, Shuai, Bastle, Ryan M., Thompson, Robert E., Stransky, Stephanie, Ramakrishnan, Aarthi, Cunningham, Ashley M., Dutta, Sohini, Chan, Jennifer C., Di Salvo, Giuseppina, Chen, Min, Zhang, Nan, Wu, Jinghua, Fulton, Sasha L., Kong, Lingchun, Wang, Haifeng, Zhang, Baichao, Vostal, Lauren, Upad, Akhil, Dierdorff, Lauren, Shen, Li, Molina, Henrik, Sidoli, Simone, Muir, Tom W., Li, Haitao, David, Yael, Maze, Ian

Issue&Volume: 2025-01-08

Abstract: Histone H3 monoaminylations at Gln5 represent an important family of epigenetic marks in brain that have critical roles in permissive gene expression1,2,3. We previously demonstrated that serotonylation4,5,6,7,8,9,10 and dopaminylation9,11,12,13 of Gln5 of histone H3 (H3Q5ser and H3Q5dop, respectively) are catalysed by transglutaminase 2 (TG2), and alter both local and global chromatin states. Here we found that TG2 additionally functions as an eraser and exchanger of H3 monoaminylations, including H3Q5 histaminylation (H3Q5his), which displays diurnally rhythmic expression in brain and contributes to circadian gene expression and behaviour. We found that H3Q5his, in contrast to H3Q5ser, inhibits the binding of WDR5, a core member of histone H3 Lys4 (H3K4) methyltransferase complexes, thereby antagonizing methyltransferase activities on H3K4. Taken together, these data elucidate a mechanism through which a single chromatin regulatory enzyme has the ability to sense chemical microenvironments to affect the epigenetic states of cells, the dynamics of which have critical roles in the regulation of neural rhythmicity.

DOI: 10.1038/s41586-024-08371-3

Source: https://www.nature.com/articles/s41586-024-08371-3