Novel retrotransposed imprinted locus identified at human 6p25.
Novel retrotransposed imprinted locus identified at human 6p25.
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DOI：
10.1093/nar/gkr108
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发表时间：
2011-07
影响因子：
14.9
通讯作者：
Jirtle RL
中科院分区：
文献类型：
--
作者：
Zhang A;Skaar DA;Li Y;Huang D;Price TM;Murphy SK;Jirtle RL
差异甲基化区域（DMR）是印记基因内或附近的稳定表观遗传特征。我们利用这一特征，通过定量DNA甲基化分析来识别候选人印迹基因座。我们在FAM 50 B的5′端6p25.2处发现了一个独特的DMR。我们确定，有义转录起源于FAM 50 B基因座的表达从父系等位基因在所有人类组织中的研究，除了卵巢，其中的表达是双等位基因。此外，反义转录本FAM 50 B-AS被鉴定为在多种组织中从父本等位基因单等位基因表达。比较系统发育分析表明，FAM 50 B同源基因在鸡和鸭嘴兽中不存在，但在负鼠和小鼠中存在并双等位表达。这些发现表明，FAM 50 B起源于Therians后，分歧从Prototherians通过逆转录转座的基因在X染色体上。此外，我们的数据是一致的，在真兽目进化过程中获得的印记后，分歧的Glires从Euarchonta哺乳动物。FAM 50 B在睾丸生殖细胞肿瘤中表达失调，并且在睾丸腺瘤中经常发生印迹丢失，这表明FAM 50 B在精子发生和肿瘤发生中起重要作用。这些结果也强调了解释父母起源在理解6p 25相关疾病机制中的重要性。
Differentially methylated regions (DMRs) are stable epigenetic features within or in proximity to imprinted genes. We used this feature to identify candidate human imprinted loci by quantitative DNA methylation analysis. We discovered a unique DMR at the 5′-end of FAM50B at 6p25.2. We determined that sense transcripts originating from the FAM50B locus are expressed from the paternal allele in all human tissues investigated except for ovary, in which expression is biallelic. Furthermore, an antisense transcript, FAM50B-AS, was identified to be monoallelically expressed from the paternal allele in a variety of tissues. Comparative phylogenetic analysis showed that FAM50B orthologs are absent in chicken and platypus, but are present and biallelically expressed in opossum and mouse. These findings indicate that FAM50B originated in Therians after divergence from Prototherians via retrotransposition of a gene on the X chromosome. Moreover, our data are consistent with acquisition of imprinting during Eutherian evolution after divergence of Glires from the Euarchonta mammals. FAM50B expression is deregulated in testicular germ cell tumors, and loss of imprinting occurs frequently in testicular seminomas, suggesting an important role for FAM50B in spermatogenesis and tumorigenesis. These results also underscore the importance of accounting for parental origin in understanding the mechanism of 6p25-related diseases.
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作者：
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3.5
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