Determinants of expression variability.
Determinants of expression variability.
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DOI：
10.1093/nar/gkt1364
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发表时间：
2014-04
影响因子：
14.9
通讯作者：
Hannenhalli S
中科院分区：
文献类型：
--
作者：
Alemu EY;Carl JW Jr;Corrada Bravo H;Hannenhalli S
个体间的组织特异性表达变异性（EV）的量是基因的基本特征，并且被认为部分是在功能限制下进化的。然而，EV的决定因素和功能影响才刚刚开始研究。我们的分析的基础上多个表达谱在41个主要的人类组织显示，一个基因的EV是显着相关的一些功能有关的基因组，表观基因组，监管，多态性，功能，结构和网络特征的基因。我们发现（i）基因的EV部分由其基因组背景编码，并进一步受表观基因组的影响;（ii）强启动子诱导较少的可变表达;（iii）较少可变的基因位点在针对拷贝数多态性的纯化选择下进化;（iv）编码固有无序或高度相互作用蛋白质的基因表现出较低的可变性;和（v）具有较少可变表达的基因富含管家功能，而具有高度可变表达的基因倾向于在发育和细胞外应答中起作用，并且与人类疾病相关。因此，我们的分析揭示了一些潜在的介质以及EV的功能和进化相关性，并提供了新的见解，在真核基因表达的固有变异性。
The amount of tissue-specific expression variability (EV) across individuals is an essential characteristic of a gene and believed to have evolved, in part, under functional constraints. However, the determinants and functional implications of EV are only beginning to be investigated. Our analyses based on multiple expression profiles in 41 primary human tissues show that a gene’s EV is significantly correlated with a number of features pertaining to the genomic, epigenomic, regulatory, polymorphic, functional, structural and network characteristics of the gene. We found that (i) EV of a gene is encoded, in part, by its genomic context and is further influenced by the epigenome; (ii) strong promoters induce less variable expression; (iii) less variable gene loci evolve under purifying selection against copy number polymorphisms; (iv) genes that encode inherently disordered or highly interacting proteins exhibit lower variability; and (v) genes with less variable expression are enriched for house-keeping functions, while genes with highly variable expression tend to function in development and extra-cellular response and are associated with human diseases. Thus, our analysis reveals a number of potential mediators as well as functional and evolutionary correlates of EV, and provides new insights into the inherent variability in eukaryotic gene expression.
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影响因子：
6.8
作者：
Dunker, A. Keith;Silman, Israel;Sussman, Joel L.
通讯作者：
Sussman, Joel L.
影响因子：
7
作者：
Battle A;Mostafavi S;Zhu X;Potash JB;Weissman MM;McCormick C;Haudenschild CD;Beckman KB;Shi J;Mei R;Urban AE;Montgomery SB;Levinson DF;Koller D
通讯作者：
Koller D
DOI：
10.1073/pnas.1003975107
发表时间：
2010-07-27
影响因子：
11.1
作者：
Kittisopikul, Mark;Suel, Gurol M.
通讯作者：
Suel, Gurol M.
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
2.5
作者：
Levy, S;Hannenhalli, S
通讯作者：
Hannenhalli, S