Wang Q, Stacy T, Miller J D, Lewis A F, Gu T L, Huang X, Bushweller J H, Bories J C, Alt F W, Ryan G, Liu P P, Wynshaw-Boris A, Binder M, Marín-Padilla M, Sharpe A H, Speck N A
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Cell. 1996 Nov 15;87(4):697-708. doi: 10.1016/s0092-8674(00)81389-6.
The CBFbeta subunit is the non-DNA-binding subunit of the heterodimeric core-binding factor (CBF). CBFbeta associates with DNA-binding CBFalpha subunits and increases their affinity for DNA. Genes encoding the CBFbeta subunit (CBFB) and one of the CBFalpha subunits (CBFA2, otherwise known as AML1) are the most frequent targets of chromosomal translocations in acute leukemias in humans. We and others previously demonstrated that homozygous disruption of the mouse Cbfa2 (AML1) gene results in embryonic lethality at midgestation due to hemorrhaging in the central nervous system and blocks fetal liver hematopoiesis. Here we demonstrate that homozygous mutation of the Cbfb gene results in the same phenotype. Our results demonstrate that the CBFbeta subunit is required for CBFalpha2 function in vivo.
CBFβ亚基是异二聚体核心结合因子（CBF）的非DNA结合亚基。CBFβ与DNA结合的CBFα亚基结合，并增加它们对DNA的亲和力。编码CBFβ亚基（CBFB）和其中一个CBFα亚基（CBFA2，也称为AML1）的基因是人类急性白血病中最常见的染色体易位靶点。我们和其他人之前证明，小鼠Cbfa2（AML1）基因的纯合缺失会导致妊娠中期胚胎致死，原因是中枢神经系统出血，并阻断胎儿肝脏造血。在这里，我们证明Cbfb基因的纯合突变会导致相同的表型。我们的结果表明，CBFβ亚基是CBFα2在体内发挥功能所必需的。
