Voss Anne K, Collin Caitlin, Dixon Mathew P, Thomas Tim
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
Dev Cell. 2009 Nov;17(5):674-86. doi: 10.1016/j.devcel.2009.10.006.
We report that embryos deficient in the histone acetyltransferase Moz (Myst3/Kat6a) show histone H3 lysine 9 (H3K9) hypoacetylation, corresponding H3K9 hypermethylation, and reduced transcription at Hox gene loci. Consistent with an observed caudal shift in Hox gene expression, segment identity is shifted anteriorly, such that Moz-deficient mice show a profound homeotic transformation of the axial skeleton and the nervous system. Intriguingly, histone acetylation defects are relatively specific to H3K9 at Hox loci, as neither Hox H3K14 acetylation nor bulk H3K9 acetylation levels throughout the genome are strongly affected; H4K16 acetylation actually increases in the absence of Moz. H3K9 hypoacetylation, Hox gene repression, and the homeotic transformation caused by lack of Moz are all reversed by treatment with retinoic acid (RA). In conclusion, our data show that Moz regulates H3K9 acetylation at Hox gene loci and that RA can act independently of Moz to establish specific Hox gene expression boundaries.
我们报告称，缺乏组蛋白乙酰转移酶Moz（Myst3/Kat6a）的胚胎表现出组蛋白H3赖氨酸9（H3K9）低乙酰化、相应的H3K9高甲基化以及Hox基因座处转录减少。与观察到的Hox基因表达的尾部移位一致，节段身份向前移位，使得缺乏Moz的小鼠在轴骨骼和神经系统中表现出深刻的同源异型转化。有趣的是，组蛋白乙酰化缺陷相对特异地存在于Hox基因座的H3K9，因为整个基因组中的Hox H3K14乙酰化或整体H3K9乙酰化水平均未受到强烈影响；在缺乏Moz的情况下，H4K16乙酰化实际上增加。缺乏Moz导致的H3K9低乙酰化、Hox基因抑制和同源异型转化都可通过视黄酸（RA）处理而逆转。总之，我们的数据表明，Moz调节Hox基因座处的H3K9乙酰化，并且RA可以独立于Moz发挥作用以建立特定的Hox基因表达边界。
