Chamberlain S J, Brannan C I
Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida 32610, USA.
Genomics. 2001 May 1;73(3):316-22. doi: 10.1006/geno.2001.6543.
The imprinted UBE3A gene exhibits maternal-only expression in specific cell types in the brain, but exhibits biallelic expression in other cell types. UBE3A is located adjacent to a cluster of imprinted, paternally expressed genes that are known to be positively regulated by the Prader-Willi syndrome imprinting center (PWS-IC). Here, we examined the effect of the PWS-IC on the UBE3A locus. Using intersubspecific crosses, we found that deletion of the PWS-IC causes an upregulation of the paternal Ube3a allele. This indicates that unlike its positive effect on all the other paternally expressed transcripts in the region, the PWS-IC negatively regulates the levels of paternal UBE3A. Interestingly, we found that like the human UBE3A locus, the murine Ube3a locus includes an imprinted, paternally expressed antisense transcript. We show that this paternal antisense transcript is positively regulated by the PWS-IC. These results are consistent with a model in which the PWS-IC mediates activation and maintenance of paternal gene expression in the 15q11-q13 region, with repression of the paternal UBE3A gene occurring as an indirect result of expression of the antisense transcript.
印记基因UBE3A在大脑中的特定细胞类型中仅呈现母源表达，但在其他细胞类型中呈现双等位基因表达。UBE3A位于一组印记的父源表达基因簇附近，已知这些基因受普拉德-威利综合征印记中心（PWS-IC）正向调控。在此，我们研究了PWS-IC对UBE3A基因座的影响。通过种间杂交，我们发现删除PWS-IC会导致父源Ube3a等位基因上调。这表明，与它对该区域所有其他父源表达转录本的正向作用不同，PWS-IC对父源UBE3A的水平起负向调控作用。有趣的是，我们发现与人类UBE3A基因座一样，小鼠Ube3a基因座包含一个印记的、父源表达的反义转录本。我们表明，这个父源反义转录本受PWS-IC正向调控。这些结果与一个模型一致，即PWS-IC介导15q1-q13区域父源基因表达的激活和维持，而父源UBE3A基因的抑制是反义转录本表达的间接结果。
