Genetic architecture of protein expression and its regulation in the mouse brain

文献类型： 外文期刊

第一作者： Erickson, Alyssa

作者： Erickson, Alyssa;Li, Ling;Even, Zachary;Huang, He;Wang, Xusheng;Zhou, Suiping;Peng, Junmin;Luo, Jie;Huang, Xin;Xu, Hai-Ming;Lu, Lu

作者机构：

关键词： Proteome; Mouse; Brain; Protein expression; Allele-specific expression; Protein regulation; Mass spectrometry

期刊名称：BMC GENOMICS （ 影响因子：4.547； 五年影响因子：4.931 ）

ISSN： 1471-2164

年卷期： 2021 年 22 卷 1 期

页码：

收录情况： SCI

摘要： Background Natural variation in protein expression is common in all organisms and contributes to phenotypic differences among individuals. While variation in gene expression at the transcript level has been extensively investigated, the genetic mechanisms underlying variation in protein expression have lagged considerably behind. Here we investigate genetic architecture of protein expression by profiling a deep mouse brain proteome of two inbred strains, C57BL/6 J (B6) and DBA/2 J (D2), and their reciprocal F1 hybrids using two-dimensional liquid chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) technology. Results By comparing protein expression levels in the four mouse strains, we observed 329 statistically significant differentially expressed proteins between the two parental strains and characterized the genetic basis of protein expression. We further applied a proteogenomic approach to detect variant peptides and define protein allele-specific expression (pASE), identifying 33 variant peptides with cis-effects and 17 variant peptides showing trans-effects. Comparison of regulation at transcript and protein levels show a significant divergence. Conclusions The results provide a comprehensive analysis of genetic architecture of protein expression and the contribution of cis- and trans-acting regulatory differences to protein expression.

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