KAT6B overexpression rescues embryonic lethality in homozygous null KAT6A mice restoring vitality and normal lifespan [CUT&TAG]

Closely related genes typically display common essential functions but also functional diversification, ensuring retention of both genes throughout evolution. The histone lysine acetyltransferases KAT6A (MOZ) and KAT6B (QKF/MORF), sharing identical protein domain structure, are mutually exclusive catalytic subunits of a multiprotein complex. Mutations in either KAT6A or KAT6B result in congenital intellectual disability disorders in human patients. In mice, loss of function of either gene results in distinct, severe phenotypic consequences. In this dataset, we investigate the effects of overexpression of KAT6B on the histone acetylation changes caused by loss of KAT6A in mouse embryonic fibroblasts. We show that Kat6b overexpression restores acetylation at histone H3 lysines 23 in Kat6a mutant mouse primary embryonic fibroblasts. Overall design: CUT&Tag results detecting histone H3 lysine 23 acetylation in (H3K23ac) in primary mouse embryonic fibroblasts isolated from E14.5 Kat6a+/+Kat6b+/+, Kat6a–/–Kat6b+/+, Kat6a–/–Tg(Kat6b) and Kat6a+/+Tg(Kat6b) foetuses. N = 4 foetuses per genotype.

亲缘关系紧密的基因通常兼具共同的核心功能与功能分化，从而确保二者在演化过程中均得以保留。组蛋白赖氨酸乙酰转移酶（histone lysine acetyltransferases）KAT6A（MOZ）与KAT6B（QKF/MORF）拥有完全一致的蛋白质结构域，二者同为某一多蛋白复合物中互斥存在的催化亚基。人类体内KAT6A或KAT6B发生突变时，会引发先天性智力障碍疾病。在小鼠模型中，任一基因的功能缺失都会引发显著且严重的表型异常。本数据集旨在探究KAT6B过表达对小鼠胚胎成纤维细胞中因KAT6A缺失所引发的组蛋白乙酰化变化的调控效应。本研究证实，在KAT6A突变的小鼠原代胚胎成纤维细胞中，KAT6B过表达可恢复组蛋白H3赖氨酸23位点的乙酰化水平。实验整体设计：采用CUT&Tag技术检测分离自E14.5天四种基因型胎鼠的原代小鼠胚胎成纤维细胞中组蛋白H3赖氨酸23乙酰化（H3K23ac）水平，四种基因型分别为Kat6a+/+Kat6b+/+、Kat6a–/–Kat6b+/+、Kat6a–/–Tg(Kat6b)与Kat6a+/+Tg(Kat6b)；每组基因型包含4只胎鼠。