Department of Health Sciences, Università Degli Studi di Milano, 20142 Milan, Italy.
"Aldo Ravelli" Center for Neurotechnology and Experimental Brain Therapeutics, Università Degli Studi di Milano, 20142 Milan, Italy.
Genes (Basel). 2022 Mar 15;13(3):514. doi: 10.3390/genes13030514.
(Lysine methyltransferase 2A) is a member of the epigenetic machinery, encoding a lysine methyltransferase responsible for the transcriptional activation through lysine 4 of histone 3 (H3K4) methylation. has a crucial role in gene expression, thus it is associated to pathological conditions when found mutated. germinal mutations are associated to Wiedemann-Steiner syndrome and also in patients with initial clinical diagnosis of several other chromatinopathies (i.e., Coffin-Siris syndromes, Kabuki syndrome, Cornelia De Lange syndrome, Rubinstein-Taybi syndrome), sharing an overlapping phenotype. On the other hand, somatic mutations have been reported in several tumors, mainly blood malignancies. Due to its evolutionary conservation, the role of KMT2A in embryonic development, hematopoiesis and neurodevelopment has been explored in different animal models, and in recent decades, epigenetic treatments for disorders linked to KMT2A dysfunction have been extensively investigated. To note, pharmaceutical compounds acting on tumors characterized by mutations have been formulated, and even nutritional interventions for chromatinopathies have become the object of study due to the role of microbiota in epigenetic regulation.
赖氨酸甲基转移酶 2A（Lysine methyltransferase 2A）是表观遗传学机制的成员，编码一种赖氨酸甲基转移酶，负责通过组蛋白 3（H3）赖氨酸 4 的甲基化实现转录激活。在基因表达中具有关键作用，因此当发现突变时与病理状况相关。胚系突变与 Wiedemann-Steiner 综合征有关，也与具有几种其他染色质病（即 Coffin-Siris 综合征、Kabuki 综合征、Cornelia De Lange 综合征、Rubinstein-Taybi 综合征）初始临床诊断的患者有关，具有重叠的表型。另一方面，已在几种肿瘤中报道了体细胞突变，主要是血液恶性肿瘤。由于其进化保守性，KMT2A 在胚胎发育、造血和神经发育中的作用已在不同的动物模型中进行了探索，并且在过去几十年中，针对与 KMT2A 功能障碍相关的疾病的表观遗传治疗已得到广泛研究。值得注意的是，已经针对具有 突变的肿瘤制定了作用于该基因的药物化合物，甚至由于微生物组在表观遗传调控中的作用，针对染色质病的营养干预也成为了研究对象。
