Expression of human NAA11 (ARD1B) gene is tissue-specific and is regulated by DNA methylation.

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.