Parent-of-Origin Allelic Expression in the Mouse Cerebellum

The maternal and paternal genomes play different roles in mammalian brains as a result of genomic imprinting, an epigenetic regulation leading to differential expression of the parental alleles of some genes. Here we investigate genomic imprinting in the cerebellum using a newly developed Bayesian statistical model that provides unprecedented transcript-level resolution. We uncover 160 imprinted transcripts, including 41 novel and independently validated imprinted genes. Strikingly, many genes exhibit parentally biased -rather than monoallelic- expression, with different magnitudes according to age, organ, and brain region. Developmental changes in parental bias and overall gene expression are strongly correlated, suggesting combined roles in regulating gene dosage. These findings reveal the remarkable complexity of genomic imprinting, with important implications for understanding the normal and diseased brain. 48 samples of F1 mouse hybrids produced by crossing C57Bl/6J males with Cast/EiJ females (denoted as F1i) and reciprocally crossing Cast/EiJ males and C57Bl/6J famales (denoted as F1r).由于基因组印记（genomic imprinting）——一种可导致部分基因的亲本等位基因产生差异表达的表观遗传调控机制——哺乳动物大脑中父本与母本基因组发挥着截然不同的作用。本研究借助一种全新开发的贝叶斯统计模型，以空前的转录本级分辨率对小脑中的基因组印记展开探究。我们共鉴定出160个印记转录本，其中包含41个经独立验证的新发现印记基因。值得注意的是，多数基因呈现亲本偏向性而非单等位基因表达，且偏向程度会随年龄、器官以及脑区的不同而发生变化。亲本偏向性与整体基因表达的发育变化呈现强相关性，提示二者在调控基因剂量过程中具有协同作用。上述发现揭示了基因组印记的显著复杂性，对于理解正常与病变大脑均具有重要价值。本研究共使用48份F1小鼠杂交样本：一组由C57Bl/6J雄性小鼠与Cast/EiJ雌性小鼠杂交获得（记为F1i），另一组为反向杂交（即Cast/EiJ雄性与C57Bl/6J雌性小鼠杂交，记为F1r）。