Epigenetic regulation of olfactory receptor gene expression by the Myb-MuvB/dREAM complex
Epigenetic regulation of olfactory receptor gene expression by the Myb-MuvB/dREAM complex
复制标题
DOI：
10.1101/gad.201665.112
复制
发表时间：
2012-11-15
影响因子：
10.5
通讯作者：
Ray, Anandasankar
中科院分区：
文献类型：
--
作者：
Sim, Choon Kiat;Perry, Sarah;Ray, Anandasankar
在哺乳动物和昆虫中，嗅觉神经元通常会选择一个单一的嗅觉受体，并抑制大受体家族的其余成员。在这里，我们证明了一个保守的多蛋白复合体Myb-MuvB(MMB)/DREAM，在介导果蝇二氧化碳(CO2)受体基因(Gr63a/Gr21a)的神经元特异性表达方面发挥了重要作用。该复合体中Myb的活性是Gr63a/Gr21a表达所必需的，它与组蛋白甲基转移酶SU(Var)3-9相反。与此一致，我们观察到受体基因位点上的抑制性二甲基化H3K9修饰，表明了一种沉默受体基因表达的机制。相反，其他复杂成员，Mip120(Myb相互作用蛋白120)和E2F2，需要在不适当的神经元中抑制Gr63a。突变体的错误表达伴随着受体基因座上活性染色质的H3K4me3标记的增加。与周围神经元相比，表达CO2受体的神经元细胞核中抑制亚单位Mip120的水平降低，Myb的水平上升，这表明该复合体的活性可以以细胞特异性的方式进行调节。我们的证据表明了一种模型，在该模型中，嗅觉受体受表观遗传调控，MMB/DREAM复合体在指定、维持和调节受体到神经元的映射中发挥关键作用。
In both mammals and insects, an olfactory neuron will usually select a single olfactory receptor and repress remaining members of large receptor families. Here we show that a conserved multiprotein complex, Myb-MuvB (MMB)/dREAM, plays an important role in mediating neuron-specific expression of the carbon dioxide (CO2) receptor genes (Gr63a/Gr21a) in Drosophila. Activity of Myb in the complex is required for expression of Gr63a/Gr21a and acts in opposition to the histone methyltransferase Su(var)3-9. Consistent with this, we observed repressive dimethylated H3K9 modifications at the receptor gene loci, suggesting a mechanism for silencing receptor gene expression. Conversely, other complex members, Mip120 (Myb-interacting protein 120) and E2F2, are required for repression of Gr63a in inappropriate neurons. Misexpression in mutants is accompanied by an increase in the H3K4me3 mark of active chromatin at the receptor gene locus. Nuclei of CO2 receptor-expressing neurons contain reduced levels of the repressive subunit Mip120 compared with surrounding neurons and increased levels of Myb, suggesting that activity of the complex can be regulated in a cell-specific manner. Our evidence suggests a model in which olfactory receptors are regulated epigenetically and the MMB/dREAM complex plays a critical role in specifying, maintaining, and modulating the receptor-to-neuron map.