The histone lysine acetyltransferase KAT6B (MYST4, MORF, QKF) is the target of recurrent chromosomal translocations causing hematological malignancies with poor prognosis. Using germline deletion and overexpression in mice, we determined the role of KAT6B in the hematopoietic system. We found that KAT6B sustained the fetal hematopoietic stem cell pool but did not affect viability or differentiation. KAT6B was essential for normal levels of histone H3 lysine 9 (H3K9) acetylation but not for a previously proposed target, H3K23. Compound heterozygosity of and the closely related gene, abolished hematopoietic reconstitution after transplantation. KAT6B and KAT6A cooperatively promoted transcription of genes regulating hematopoiesis, including the cluster, , family, and . In conclusion, we identified the hematopoietic processes requiring and showed that KAT6B and KAT6A synergistically promoted HSC development, function, and transcription. Our findings are pertinent to current clinical trials testing KAT6A/B inhibitors as cancer therapeutics.

中文翻译：

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组蛋白乙酰转移酶 KAT6B 是造血干细胞发育和功能所必需的

组蛋白赖氨酸乙酰转移酶 KAT6B（MYST4、MORF、QKF）是反复染色体易位的靶标，可导致预后不良的血液恶性肿瘤。通过在小鼠中进行种系缺失和过度表达，我们确定了 KAT6B 在造血系统中的作用。我们发现 KAT6B 维持胎儿造血干细胞库，但不影响活力或分化。 KAT6B 对于正常水平的组蛋白 H3 赖氨酸 9 (H3K9) 乙酰化至关重要，但对于之前提出的靶标 H3K23 则不然。与密切相关的基因的复合杂合性，废除了移植后的造血重建。 KAT6B 和 KAT6A 协同促进造血调节基因的转录，包括簇、 、 家族和 。总之，我们确定了所需的造血过程，并表明 KAT6B 和 KAT6A 协同促进 HSC 的发育、功能和转录。我们的研究结果与当前测试 KAT6A/B 抑制剂作为癌症治疗药物的临床试验相关。