Multivariable regulation of gene expression plasticity in metazoans
Multivariable regulation of gene expression plasticity in metazoans
复制标题
后生动物基因表达可塑性的多变量调控
DOI：
10.1098/rsob.190150
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发表时间：
2019-07
期刊：
影响因子：
5.8
通讯作者：
Du Z.
中科院分区：
文献类型：
--
作者：
Xiao L;Zhao Z;He F;Du Z.
基因的一个重要能力是表达水平的快速变化，以应对环境，称为表达响应性或可塑性。阐明决定表达可塑性的基因组机制对于理解表型可塑性、适应性和适应性的分子基础至关重要。在这项研究中，我们通过整合在大量遗传和环境条件下表达水平的变化，系统地量化了四个后生动物物种的基因表达可塑性。由此，我们证明了表达可塑性衡量了基因表达的一个明显特征，该特征与其他研究良好的特征是正交的，包括基因表达水平和组织特异性/广度。表达可塑性在物种间是保守的，具有重要的生理意义。表达可塑性的大小与基因功能高度相关，高可塑性的基因与疾病易感性有关。全基因组分析发现，许多保守的启动子顺式元件、反式作用因子(如CTCF)和基因体组蛋白修饰(H3K36me3、H3K79me2和H4K20me1)与表达可塑性显著相关。对扰动实验中表达变化的分析进一步证实了特定转录因子和组蛋白修饰的因果作用。综上所述，这项工作揭示了后生动物基因表达可塑性的一般特性、生理意义和多变量调控，扩展了对基因调控的机制理解。
An important capacity of genes is the rapid change of expression levels to cope with the environment, known as expression responsiveness or plasticity. Elucidating the genomic mechanisms determining expression plasticity is critical for understanding the molecular basis of phenotypic plasticity, fitness and adaptation. In this study, we systematically quantified gene expression plasticity in four metazoan species by integrating changes of expression levels under a large number of genetic and environmental conditions. From this, we demonstrated that expression plasticity measures a distinct feature of gene expression that is orthogonal to other well-studied features, including gene expression level and tissue specificity/broadness. Expression plasticity is conserved across species with important physiological implications. The magnitude of expression plasticity is highly correlated with gene function and genes with high plasticity are implicated in disease susceptibility. Genome-wide analysis identified many conserved promotercis-elements,trans-acting factors (such as CTCF), and gene body histone modifications (H3K36me3, H3K79me2 and H4K20me1) that are significantly associated with expression plasticity. Analysis of expression changes in perturbation experiments further validated a causal role of specific transcription factors and histone modifications. Collectively, this work reveals the general properties, physiological implications and multivariable regulation of gene expression plasticity in metazoans, extending the mechanistic understanding of gene regulation.
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影响因子：
8.8
作者：
Core LJ;Waterfall JJ;Gilchrist DA;Fargo DC;Kwak H;Adelman K;Lis JT
通讯作者：
Lis JT
影响因子：
7
作者：
Wang J;Zhuang J;Iyer S;Lin X;Whitfield TW;Greven MC;Pierce BG;Dong X;Kundaje A;Cheng Y;Rando OJ;Birney E;Myers RM;Noble WS;Snyder M;Weng Z
通讯作者：
Weng Z
DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
14.9
作者：
Howe KL;Bolt BJ;Cain S;Chan J;Chen WJ;Davis P;Done J;Down T;Gao S;Grove C;Harris TW;Kishore R;Lee R;Lomax J;Li Y;Muller HM;Nakamura C;Nuin P;Paulini M;Raciti D;Schindelman G;Stanley E;Tuli MA;Van Auken K;Wang D;Wang X;Williams G;Wright A;Yook K;Berriman M;Kersey P;Schedl T;Stein L;Sternberg PW
通讯作者：
Sternberg PW
影响因子：
4.5
作者：
Rechtsteiner A;Ercan S;Takasaki T;Phippen TM;Egelhofer TA;Wang W;Kimura H;Lieb JD;Strome S
通讯作者：
Strome S