Pohlers Michael, Calabrese J Mauro, Magnuson Terry
Department of Genetics, the Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599.
Department of Genetics, the Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599
G3 (Bethesda). 2014 Aug 21;4(10):1981-9. doi: 10.1534/g3.114.012260.
Small noncoding RNAs play several roles in regulating gene expression. In the nucleus, small RNA-Argonaute complexes recruit epigenetic modifying activities to genomic sites. This pathway has been described in mammals primarily for the germline; however, its role in somatic cells is less characterized. Here, we describe in human somatic cells a potential link between the expression of small RNAs from the macrosatellite DXZ4 and Argonaute-dependent DNA methylation of this locus. DXZ4 was found to express a wide range of small RNAs potentially representing several classes of small RNAs. A subpopulation of these RNAs is bound by Argonaute. Moreover, we show AGO association with DXZ4 and that the Argonaute proteins AGO-1 and PIWIL4 may play a role in DNA methylation of DXZ4. We hypothesize that the RNAs are involved in Argonaute-dependent methylation of DXZ4 DNA.
小非编码RNA在调节基因表达中发挥多种作用。在细胞核中,小RNA-AGO蛋白复合物将表观遗传修饰活性招募到基因组位点。这条途径在哺乳动物中主要是针对生殖系进行描述的;然而,其在体细胞中的作用尚未得到充分表征。在这里,我们在人类体细胞中描述了来自大卫星DXZ4的小RNA表达与该位点的AGO蛋白依赖性DNA甲基化之间的潜在联系。发现DXZ4表达多种小RNA,可能代表几类小RNA。这些RNA的一个亚群与AGO蛋白结合。此外,我们展示了AGO蛋白与DXZ4的关联,并且AGO-1和PIWIL4这两种AGO蛋白可能在DXZ4的DNA甲基化中发挥作用。我们推测这些RNA参与了DXZ4 DNA的AGO蛋白依赖性甲基化。