MLL targets SET domain methyltransferase activity to Hox gene promoters
MLL targets SET domain methyltransferase activity to Hox gene promoters
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DOI：
10.1016/s1097-2765(02)00741-4
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发表时间：
2002-11-01
期刊：
影响因子：
16
通讯作者：
Hess, JL
中科院分区：
文献类型：
--
作者：
Milne, TA;Briggs, SD;Hess, JL
MLL是三胸果蝇的人类同源物，在哺乳动物胚胎中维持Hox基因表达，并在人类白血病中重排，导致Hox基因失调。MLL或MLL融合蛋白如何调节基因表达仍不清楚。我们表明，MLL调节目标Hox基因的表达，通过直接结合到启动子序列。我们进一步表明，MILL SET域是一个组蛋白H3赖氨酸4-特异性甲基转移酶，其活性与乙酰化H3肽刺激。这种甲基化酶活性与体内Hox基因激活和H3（Lys 4）顺式调控序列甲基化有关。致白血病的MLL融合蛋白激活Hox表达对组蛋白甲基化没有影响，这表明MLL和MLL融合蛋白的基因调控机制不同。
MLL, the human homolog of Drosophila trithorax, maintains Hox gene expression in mammalian embryos and is rearranged in human leukemias resulting in Hox gene deregulation. How MLL or MLL fusion proteins regulate gene expression remains obscure. We show that MLL regulates target Hox gene expression through direct binding to promoter sequences. We further show that the MILL SET domain is a histone H3 lysine 4-specific methyltransferase whose activity is stimulated with acetylated H3 peptides. This methylase activity is associated with Hox gene activation and H3 (Lys4) methylation at cis-regulatory sequences in vivo. A leukemogenic MLL fusion protein that activates Hox expression had no effect on histone methylation, suggesting a distinct mechanism for gene regulation by MLL and MLL fusion proteins.