Inserm, U1016, Institut Cochin, Paris, France.
Epigenetics. 2012 Sep;7(9):1079-90. doi: 10.4161/epi.21495. Epub 2012 Aug 16.
Genomic imprinting characterizes genes with a monoallelic expression, which is dependent on the parental origin of each allele. Approximately 150 imprinted genes are known to date, in humans and mice but, though computational searches have tried to extract intrinsic characteristics of these genes to identify new ones, the existing list is probably far from being comprehensive. We used a high-throughput strategy by diverting the classical use of genotyping microarrays to compare the genotypes of mRNA/cDNA vs. genomic DNA to identify new genes presenting monoallelic expression, starting from human placental material. After filtering of data, we obtained a list of 1,082 putative candidate monoallelic SNPs located in more than one hundred candidate genes. Among these, we found known imprinted genes, such as IPW, GRB10, INPP5F and ZNF597, which contribute to validate the approach. We also explored some likely candidates of our list and identified seven new imprinted genes, including ZFAT, ZFAT-AS1, GLIS3, NTM, MAGI2, ZC3H12Cand LIN28B, four of which encode zinc finger transcription factors. They are, however, not imprinted in the mouse placenta, except for Magi2. We analyzed in more details the ZFAT gene, which is paternally expressed in the placenta (as ZFAT-AS1, a non-coding antisense RNA) but biallelic in other tissues. The ZFAT protein is expressed in endothelial cells, as well as in syncytiotrophoblasts. The expression of this gene is, moreover, downregulated in placentas from complicated pregnancies. With this work we increase by about 10% the number of known imprinted genes in humans.
基因组印迹是指基因的单等位基因表达,这种表达依赖于每个等位基因的亲本来源。目前已知人类和小鼠中有大约 150 个印迹基因,但尽管计算搜索尝试提取这些基因的内在特征来识别新的基因,但现有的列表可能远非全面。我们使用了一种高通量策略,通过改变基因分型微阵列的经典用途,将 mRNA/cDNA 与基因组 DNA 的基因型进行比较,从人胎盘材料中鉴定出具有单等位基因表达的新基因。在数据过滤后,我们获得了 1082 个候选单等位基因 SNP 的列表,这些 SNP 位于 100 多个候选基因中。在这些基因中,我们发现了已知的印迹基因,如 IPW、GRB10、INPP5F 和 ZNF597,这些基因有助于验证该方法。我们还探索了我们列表中的一些可能的候选基因,并鉴定了七个新的印迹基因,包括 ZFAT、ZFAT-AS1、GLIS3、NTM、MAGI2、ZC3H12C 和 LIN28B,其中四个编码锌指转录因子。然而,除了 Magi2 之外,它们在小鼠胎盘上没有印迹。我们更详细地分析了 ZFAT 基因,该基因在胎盘上呈父系表达(作为非编码反义 RNA ZFAT-AS1),但在其他组织中呈双等位基因表达。ZFAT 蛋白在血管内皮细胞和合体滋养层细胞中表达。此外,该基因在复杂妊娠的胎盘中的表达下调。通过这项工作,我们将人类已知的印迹基因数量增加了约 10%。