【摘 要】
：
Enhancers are critical cis-regulatory elements that regulate spatiotemporal gene expression and control cell fates.However,the identification of enhancers in native cellular contexts still remains a challenge.Here,we develop an inducible CRISPR activation
【机 构】
：
State Key Laboratory of Experimental Hematology,The Province and Ministry Co-sponsored Collaborative
论文部分内容阅读
Enhancers are critical cis-regulatory elements that regulate spatiotemporal gene expression and control cell fates.However,the identification of enhancers in native cellular contexts still remains a challenge.Here,we develop an inducible CRISPR activation (CRISPRa) system by transgenic expression of doxycycline (Dox)-inducible dCas9-VPR in mouse embryonic stem cells (iVPR ESC).With this line,a simple introduction of specific guide RNAs targeting promoters or enhancers allows us to realize the effect of CRISPRa in an inducible,reversible,and Dox concentration-dependent manner.Taking advantage of this system,we induce tiled CRISPRa across genomic regions (105 kilobases) surrounding T (Brachyury),one of the key mesodermal development regulator genes.Moreover,we identify several CRISPRa-responsive elements with chromatin features of putative enhancers,including a region the homologous sequence in which humans harbors a body height risk variant.Genetic deletion of this region in ESC does affect subsequent T gene activation and osteogenic differentiation.Therefore,our inducible CRISPRa ESC line provides a convenient platform for high-throughput screens of putative enhancers.
其他文献
区域工业发展与水资源,能源,环境是一个相互影响的整体系统,合理测度我国区域工业全要素水-能-环境(Water-Energy-Environment,简称WEE)效率对于实现新时代我国工业经济高质量发展具有重要意义.文章在系统考虑水资源-能源-污染物三者之间关系的基础上,构建全要素WEE效率的非径向数据包络分析(DEA)评价模型,进而研究2011-2017年我国区域工业的全要素WEE整体及个体表现.研究发现:我国工业WEE效率的平均水平为0.728,东部地区的WEE整体表现以及其水,能,环境效率的个体表现均
多个承运商协同完成农产品运输时,后半程承运商谎报保鲜水平造成冷链断链.针对这一问题,在事前支付与事后支付两种方式下,构建了集成服务商和承运商的主从博弈模型,求解出了最优保鲜水平和最优接单量,据此研究了集成服务商的承运商选择策略,重点分析了谎报程度与服务价格的保鲜水平敏感性对最优结果的影响.结论 表明,前半程与后半程承运商承诺保鲜水平相等时,集成服务商选择分散决策的事后支付方式及事前支付方式下存在特定谎报范围的承运商会优于承运商联盟,否则选择承运商联盟.在事前支付方式下,只要后半程承运商谎报的保鲜水平高于前
针对损失函数为最小一乘函数的回归问题,研究其基数罚问题与MCP (minimax concave penalty)松弛问题之间解的关系.首先,证明了MCP罚松弛模型解的下界性质,以此为基础分析了基数罚问题与松弛问题之间解的等价性,证明了在一定条件下两个问题具有相同的全局最优解以及最优值,此外,还证明了松弛模型的局部最优解是基数罚问题的局部最优解,在局部极小值点处松弛模型与基数罚问题的最优值是相等的.文章结果为求解稀疏最小一乘回归问题提供了理论依据和可行途径.
针对变量比较少的判别分析问题,讨论了一种基于变量择优的Fisher逐步判别分析方法.在Fisher判别分析方法和变量空间的多项式扩展方法的基础上,该方法结合文中定义的判别效率函数,给出了挑选变量的准则.为了检验新方法的效果,分别通过一个实例、5个UCI数据集和3个模拟数据集进行测试,并与Fisher判别分析法和Fisher逐步判别分析法的效果作对比.结果 表明,对变量比较少的判别问题,文中方法有助于提高判别模型的正确率.
Although many species have gone extinct,their genetic components might exist in extant species because of ancient hybridization.Via advances in genome sequencing and development of modern population genetics,one can find the legacy of unknown or extinct s
The formation of biomolecular condensates via liquid-liquid phase separation (LLPS) is an advantageous strategy for cells to organize subcellular compartments for diverse functions.The involvement of LLPS is more widespread and overrepresented in RNA-rela
一元MV-代数(L,(A))由MV-代数连同其上的一个一元算子(A)构成,其中(A)是一元多值谓词逻辑中任意量词的代数解释.考虑到MTL-代数是一类范围最广的基于三角模的逻辑代数,为了给一元三角模谓词逻辑中任意量词提供统一的代数语义,文章引入了一元MTL-代数,研究其基本的代数性质以及对应的滤子,证明了一元MTL-代数是一元MV-代数和一元布尔代数的自然推广.其次,基于一元滤子刻画了可表示一元MTL-代数,证明了半单一元MTL-代数的次直积表示定理,揭示了强一元MTL-代数和可表示一元MTL-代数是等价的
High altitude is an extreme environment that imposes hypoxic pressure on physiological processes,and natives living at high altitudes are more adaptive in certain physiological processes.So far,epigenetic modifications under extreme changes in hypoxic pre
As a multicellular organism,rice flourishes relying on gene expression diversity among cells of various functions.However,cellular-resolution transcriptome features are yet to be fully recognized,let alone cell-specific transcriptional responses to enviro
Southern East Asia,including Guangxi and Fujian provinces in China,is home to diverse ethnic groups,languages,and cultures.Previous studies suggest a high complexity regarding population dynamics and the history of southern East Asians.However,large-scale