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首页> 外文期刊>Molecular and Cellular Biology >The Drosophila Ortholog of MLL3 and MLL4, trithorax related, Functions as a Negative Regulator of Tissue Growth
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The Drosophila Ortholog of MLL3 and MLL4, trithorax related, Functions as a Negative Regulator of Tissue Growth

机译：与胸部相关的MLL3和MLL4的果蝇直向同源物，作为组织生长的负调节剂。

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The human MLL genes (MLL1 to MLL4) and their Drosophila orthologs, trithorax (trx) and trithorax related (trr), encode proteins capable of methylating histone H3 on lysine 4. MLL1 and MLL2 are most similar to trx, while MLL3 and MLL4 are more closely related to trr. Several MLL genes are mutated in human cancers, but how these proteins regulate cell proliferation is not known. Here we show that trr mutant cells have a growth advantage over their wild-type neighbors and display changes in the levels of multiple proteins that regulate growth and cell division, including Notch, Capicua, and cyclin B. trr mutant clones display markedly reduced levels of H3K4 monomethylation without obvious changes in the levels of H3K4 di- and trimethylation. The trr mutant phenotype resembles that of Utx, which encodes a H3K27 demethylase, consistent with the observation that Trr and Utx are found in the same protein complex. In contrast to the overgrowth displayed by trr mutant tissue, trx clones are underrepresented, express low levels of the antiapoptotic protein Diap1, and exhibit only modest changes in global levels of H3K4 methylation. Thus, in Drosophila eye imaginal discs, Trr, likely functioning together with Utx, restricts tissue growth. In contrast, Trx appears to promote cell survival.
机译：人类MLL基因（ MLL1 至 MLL4 ）及其果蝇直系同源物， trithorax （ trx ）和与三胸草 相关（ trr ），编码能够在赖氨酸4上甲基化组蛋白H3的蛋白质。MLL1和MLL2与 trx 最相似，而MLL3和MLL4与 trr 密切相关。几种MLL基因在人类癌症中发生突变，但是这些蛋白质如何调节细胞增殖尚不清楚。在这里，我们显示 trr 突变细胞比其野生型邻居具有生长优势，并且在调节生长和细胞分裂的多种蛋白质（包括Notch，Capicua和cyclin B）中显示出变化。 em> trr 突变体克隆显示H3K4单甲基化水平显着降低，而H3K4二甲基化和三甲基化水平没有明显变化。 trr 突变表型与 Utx 相似，后者编码H3K27脱甲基酶，这与观察到Trr和Utx在同一蛋白质复合物中发现的现象一致。与 trr 突变组织显示的过度生长相反， trx 克隆的代表性不足，表达的抗凋亡蛋白Diap1含量低，并且在H3K4甲基化的整体水平中仅表现出适度的变化。因此，在果蝇眼的视盘中，可能与Utx一起起作用的Trr限制了组织的生长。相反，Trx似乎促进细胞存活。

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