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SUVH1, a Su(var)3-9 family member, promotes the expression of genes targeted by DNA methylation

机译:Su(var)3-9家族成员SUVH1促进DNA甲基化靶向的基因表达

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摘要

Transposable elements are found throughout the genomes of all organisms. Repressive marks such as DNA methylation and histone H3 lysine 9 (H3K9) methylation silence these elements and maintain genome integrity. However, how silencing mechanisms are themselves regulated to avoid the silencing of genes remains unclear. Here, an anti-silencing factor was identified using a forward genetic screen on a reporter line that harbors a LUCIFERASE (LUC) gene driven by a promoter that undergoes DNA methylation. SUVH1, a Su(var)3-9 homolog, was identified as a factor promoting the expression of the LUC gene. Treatment with a cytosine methylation inhibitor completely suppressed the LUC expression defects of suvh1, indicating that SUVH1 is dispensable for LUC expression in the absence of DNA methylation. SUVH1 also promotes the expression of several endogenous genes with promoter DNA methylation. However, the suvh1 mutation did not alter DNA methylation levels at the LUC transgene or on a genome-wide scale; thus, SUVH1 functions downstream of DNA methylation. Histone H3 lysine 4 (H3K4) trimethylation was reduced in suvh1; in contrast, H3K9 methylation levels remained unchanged. This work has uncovered a novel, anti-silencing function for a member of the Su(var)3-9 family that has previously been associated with silencing through H3K9 methylation.
机译:在所有生物的整个基因组中都发现了转座因子。诸如DNA甲基化和组蛋白H3赖氨酸9(H3K9)甲基化等抑制性标记使这些元件沉默,并保持基因组完整性。但是,如何调节沉默机制以避免基因沉默仍然不清楚。在这里,使用报告基因上的正向遗传筛选方法鉴定了抗沉默因子,该报告基因系包含由经历DNA甲基化的启动子驱动的LUCIFERASE(LUC)基因。 Su(var)3-9同源物SUVH1被确定为促进LUC基因表达的因子。用胞嘧啶甲基化抑制剂处理可完全抑制suvh1的LUC表达缺陷,这表明SUVH1在不存在DNA甲基化的情况下对于LUC表达是可有可无的。 SUVH1还通过启动子DNA甲基化促进几种内源基因的表达。但是,suvh1突变不会改变LUC转基因或整个基因组范围内的DNA甲基化水平。因此,SUVH1在DNA甲基化的下游起作用。组蛋白H3赖氨酸4(H3K4)三甲基化在suvh1中减少;相反,H3K9甲基化水平保持不变。这项工作发现了Su(var)3-9家族成员的一种新颖的抗沉默功能,该功能以前与通过H3K9甲基化沉默相关。

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