Li T, Vu T H, Zeng Z L, Nguyen B T, Hayward B E, Bonthron D T, Hu J F, Hoffman A R
Medical Service and GRECC, Stanford University School of Medicine, Palo Alto, California 94304, USA.
Genomics. 2000 Nov 1;69(3):295-304. doi: 10.1006/geno.2000.6337.
The mouse Gnas gene encodes an important signal transduction protein, the alpha subunit of the stimulatory G protein, G(s). In humans, partial deficiency of G(s)alpha, the alpha subunit of G(s), results in the hormone-resistance syndrome pseudohypoparathyroidism type 1a. The mouse Gnas (and the human GNAS1) locus is transcribed from three promoter regions. Transcripts from P1, which encode Nesp55, are derived from the maternal allele only. Transcripts from P2 encode Xlalphas and are derived only from the paternal allele, while transcripts from P3 encode the alpha subunit and are from both parental alleles. The close proximity of reciprocal imprinting suggests the presence of important putative imprinting elements in this region. In this report, we demonstrate that the reciprocal imprinting occurs in normal tissues of interspecific (Mus spretus x C57BL/6) mice. Transcripts from P1 are most abundant in CNS (pons and medulla) in contrast to the more ubiquitous expression from P2 and P3. In the P1-P2 genomic region, we have identified an antisense transcript that starts 2.2 kb upstream of the P2 exon and spans the P1 region. While the P1 transcript is derived from the maternal allele, the P1-antisense (Gnas-as) is derived only from the paternal allele in most but not all tissues. Although both the Nesp55 region and the Gnas-as transcripts are present in cerebral cortex, adrenal, and spleen, Gnas-as is abundant in some tissues in which transcription from the Nesp55 region is negligible. Furthermore, the Nesp55 region transcripts remain strictly imprinted in tissues that lack Gnas-as. Our results suggest that multiple imprinting elements, including the unique Gnas-as, regulate the allelic expression of the Nesp55 region sense transcript.
小鼠Gnas基因编码一种重要的信号转导蛋白，即刺激性G蛋白G(s)的α亚基。在人类中，G(s)的α亚基G(s)α部分缺陷会导致激素抵抗综合征1a型假性甲状旁腺功能减退。小鼠Gnas（以及人类GNAS1）基因座从三个启动子区域转录。来自P1的转录本编码Nesp55，仅来自母本等位基因。来自P2的转录本编码Xlalphas，仅来自父本等位基因，而来自P3的转录本编码α亚基，来自双亲等位基因。相互印记的紧密相邻表明该区域存在重要的假定印记元件。在本报告中，我们证明相互印记发生在种间（小家鼠×C57BL/6）小鼠的正常组织中。与来自P2和P3的更普遍表达相比，来自P1的转录本在中枢神经系统（脑桥和延髓）中最为丰富。在P1 - P2基因组区域，我们鉴定出一种反义转录本，它起始于P2外显子上游2.2 kb处并跨越P1区域。虽然P1转录本来自母本等位基因，但P1反义（Gnas - as）在大多数但并非所有组织中仅来自父本等位基因。尽管Nesp55区域和Gnas - as转录本都存在于大脑皮层、肾上腺和脾脏中，但Gnas - as在一些组织中丰富，而Nesp55区域的转录在这些组织中可忽略不计。此外，Nesp55区域转录本在缺乏Gnas - as的组织中仍严格印记。我们的结果表明，包括独特的Gnas - as在内的多个印记元件调节Nesp55区域正义转录本的等位基因表达。
