Table S10 from Multivariable regulation of gene expression plasticity in metazoans

An important capacity of genes is the rapid change of expression levels to cope with 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-studies 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 promoter <i>cis</i>-elements, <i>trans</i>-acting factors (such as CFCF), 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 general properties, physiological implications and multivariable regulation of gene expression plasticity in metazoans, extending the mechanistic understanding of gene regulation.

基因的一项核心功能是通过快速改变表达水平以适应环境变化，该过程被称为表达响应性（expression responsiveness）或表达可塑性（plasticity）。阐明调控表达可塑性的基因组机制，对于解析表型可塑性、进化适合度（fitness）与适应性（adaptation）的分子基础具有关键意义。本研究整合了大量遗传与环境条件下的基因表达水平变化数据，系统定量了四种后生动物（metazoan）的基因表达可塑性水平。研究证实，表达可塑性是一类独特的基因表达特征，与基因表达水平、组织特异性/广泛性等其他已被充分研究的特征相互正交（orthogonal）。表达可塑性在物种间具有保守性，这一特性具备重要的生理学内涵。基因表达可塑性的幅度与基因功能高度相关，且高可塑性基因与疾病易感性（disease susceptibility）显著相关。全基因组分析鉴定出多种与表达可塑性显著相关的保守启动子顺式作用元件（cis-elements）、反式作用因子（trans-acting factors，如CFCF），以及定位于基因本体的组蛋白修饰（histone modifications，包括H3K36me3、H3K79me2与H4K20me1）。扰动实验中的基因表达变化分析进一步验证了特定转录因子与组蛋白修饰在调控表达可塑性中的因果作用。综上，本研究揭示了后生动物中基因表达可塑性的通用特性、生理学意义及其多变量调控机制，拓展了学界对基因调控机制的机制性理解。