PDF(Pubmed)
Abstract：
The histone lysine acetyltransferase KAT6B (MYST4, MORF, QKF) is the target of recurrent chromosomal translocations causing hematological malignancies with poor prognosis. Using Kat6b 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 Kat6b and the closely related gene, Kat6a, abolished hematopoietic reconstitution after transplantation. KAT6B and KAT6A cooperatively promoted transcription of genes regulating hematopoiesis, including the Hoxa cluster, Pbx1, Meis1, Gata family, Erg, and Flt3. In conclusion, we identified the hematopoietic processes requiring Kat6b 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.
摘要：
组蛋白赖氨酸乙酰转移酶KAT6B（MYST4，MORF，QKF)是复发性染色体易位导致恶性血液病预后不良的目标。在小鼠中使用Kat6b种系缺失和过表达，我们确定了KAT6B在造血系统中的作用.我们发现KAT6B维持了胎儿造血干细胞池，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）乙酰化是必不可少的，但对于先前提出的目标则不是，H3K23.Kat6b和密切相关基因的复合杂合性，Kat6a,移植后造血重建被废除。KAT6B和KAT6A共同促进造血调控基因的转录，包括Hoxa星团,Pbx1,Meis1,Gata家族,Erg,和Flt3。总之,我们确定了需要Kat6b的造血过程，并表明KAT6B和KAT6A协同促进了HSC的发育，函数,和转录。我们的发现与当前测试KAT6A/B抑制剂作为癌症治疗剂的临床试验有关。
