Section on Clinical and Developmental Genomics, Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health, Bethesda, MD, USA.
Epigenetics. 2011 Nov;6(11):1391-9. doi: 10.4161/epi.6.11.18125. Epub 2011 Nov 1.
NAA10 gene encodes the catalytic subunit of N(alpha)-acetyltransferase NatA that catalyzes the acetylation of the N-termini of many eukaryotic proteins. A homologous gene called NAA11 is also present in mammalian cells. hNaa10p and hNaa11p are reported to be co-expressed in human cell cultures. In mouse tissues, however, Naa11 transcripts can only be detected in gonadal tissues whereas Naa10 transcripts are present in various tissues. We re-examined the expression of NAA11 in human cell lines and expanded the test to normal as well as cancerous human tissues. Surprisingly, we did not detect the expression of NAA11 in human cell lines that previously were reported to express it. Similar to its mouse ortholog, NAA10 displayed widespread expression in human tissues. NAA11 transcripts, however, were only detected in testicular and placental tissues. The lack of NAA11 expression was also demonstrated in eight different types of human cancerous tissues. By methylation-specific polymerase chain reaction and bisulfite sequencing, we found that the absence of NAA11 expression correlated with hypermethylation of the CpG island located at the proximal promoter of NAA11 gene. We also found that the cloned NAA11 gene promoter fragment was active when introduced into non NAA11-expressing human cells and its promoter activity was lost upon in vitro DNA methylation. Taken together, our results indicate NAA11 expression is tissue-specific and is epigenetically regulated by DNA methylation.
NAA10 基因编码 N(alpha)-乙酰转移酶 NatA 的催化亚基，该酶催化许多真核蛋白质 N-末端的乙酰化。哺乳动物细胞中也存在一个同源基因，称为 NAA11。据报道，hNaa10p 和 hNaa11p 在人细胞培养物中共同表达。然而，在小鼠组织中，只能在性腺组织中检测到 Naa11 转录本，而 Naa10 转录本存在于各种组织中。我们重新检查了 NAA11 在人细胞系中的表达，并将测试扩展到正常和癌症人组织。令人惊讶的是，我们没有在以前报道表达 NAA11 的人细胞系中检测到 NAA11 的表达。与它的小鼠同源物相似，NAA10 在人类组织中广泛表达。然而，仅在睾丸和胎盘组织中检测到 NAA11 转录本。NAA11 表达的缺失也在八种不同类型的人类癌症组织中得到证实。通过甲基化特异性聚合酶链反应和亚硫酸氢盐测序，我们发现 NAA11 表达的缺失与位于 NAA11 基因近端启动子的 CpG 岛的高甲基化相关。我们还发现，当将克隆的 NAA11 基因启动子片段引入不表达 NAA11 的人细胞中时，该启动子片段具有活性，并且其启动子活性在体外 DNA 甲基化后丧失。总之，我们的结果表明 NAA11 表达具有组织特异性，并受 DNA 甲基化的表观遗传调控。
