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Importance of transcription factors in the regulation

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AbstractTranscriptionfactorsareknowntoplayakeyroleinregulatingfluxthroughpathwaysofsec-ondarymetabolism,bycontrollingthelevelsofpathwaygeneexpression.Thisregulatorymechanismseemstobeimportantfortheterpenoidpathway,asaccumulationofmanystress-inducedandstoredterpenoidsoftenfollowscoordinatedinductionofpathwaygenes.Whereasthebodyofknowledgeonregulatorsoftheflavonoidpathwayisalreadyquitelarge,transcriptionfactorscontrollingplantterpenoidaccumulationarejuststartingtobeidentified.Inadditiontotheirroleinmetaboliccontrol,transcrip-tionfactorsarealsoessentialinthedifferentiationofcellsthatproduceandaccumulateterpenoids.Inparticular,theyappeartoplayanimportantroleintheinitiationanddifferentiationofglandulartrichomes,

whichareamajorsiteofterpenoidaccumulationinplants.Wearepresentingheresomeoftherecentfindingsontheroleplayedbytheseimportantregu-latoryproteinsinsecondarymetabolismandinter-penoidbiosynthesis,aswellasthepicturethatisstartingtoemergeoftheirimplicationindifferenti-ationandmetabolicprocessesleadingtotheaccu-mulationofterpenoidsinplants.

KeywordsTranscriptionfactorÆTerpenoidÆTrichomeÆSecondaryMetabolismÆSecretorystructure

AbbreviationsTFTranscriptionFactorbHLHbasicHelix-Loop-HelixC1COLORLESS1RREDTT2,8TRANSPARENTTESTA2,8GL1GLABROUS1GL3GLABRA3PAP1,2PRODUCTIONOFANTHOCYANINPIGMENT1,2IN1INTENSIFIER1LcLEAFCOLORTTG1TRANSPARENTTESTAGLABRA1ORCA3OCTADECANOID-DERIVATIVERESPONSIVECATHARANTUSAPETALA2-DOMAINPROTEIN3

P.Broun(&)ÆY.LiuCNAPDepartmentofBiology(Area7),UniversityofYork,P.O.box373,YorkYO105YW,UKe-mail:pb22@york.ac.uk

E.QueenÆY.SchwarzÆM.L.AbenesÆM.LeibmanMendelBiotechnology,21375CabotBoulevard,Hayward94545CA,USA

M.LeibmanCenterforCancerSystemsBiologyandDepartmentofCancerBiology,Dana-FarberCancerInstitute,HarvardMedicalSchool,Boston,MA02115,USA

PhytochemRev(2006)5:27–38DOI10.1007/s11101-006-9000-x

123Importanceoftranscriptionfactorsintheregulationofplantsecondarymetabolismandtheirrelevancetothecontrolofterpenoidaccumulation

PierreBrounÆYanLiuÆEmilyQueenÆYukaSchwarzÆMaLlevaAbenesÆMarkLeibman

Received:7July2005/Accepted:25February2006/Publishedonline:1July2006ÓSpringerScience+BusinessMediaB.V.2006GRGlucocorticoidReceptorChIPChromatinImmuno-PrecipitationHMGorHMGRHydroxyMethylGlutarylCo-enzymeADXR1-deoxyxylulose-5-phosphatereducto-isomeraseDXS1-deoxyxylulose-5-phosphatesynthasePSYphytoenesynthaseIPPisopentenyldiphosphateDMAPPdimethylallyldiphosphateMEP2-C-methyl-erythritol4-phosphateTIA(mono)TerpenoidIndoleAlkaloid

IntroductionManybiologicalfactorscontributetotheaccumula-tionofsecondarymetabolitesinplants.Biochemicalandcellularfactorsinfluencebiosyntheticfluxandhowefficientlymetabolitesaretransportedandstoredintheirfinalsiteofdeposition(Winkel2004;Yazaki2005).Developmentalfactorsinfluencetheinitiationanddifferentiationofspecializedcellularstructureswherethemetabolitesaresynthesizedandaccumu-late(Turneretal.2000a).Inthecaseofvolatileterpenoids,thedevelopmentofsecretorystructuresisparticularlyimportanttometabolicoutput,astheyarerequiredformetaboliteaccumulation.Plantmor-phologyandsizecanalsohaveanimportantimpactontheoverallmetabolicoutput.Finally,environ-mentalconditionshaveastrongeffectbymodulatingplantmetabolismanddevelopment(Broecklingetal.2005;ChienandSussex1996;Zhaoetal.1998).Bothmetabolicfluxandcellulardifferentiationareknowntobecontrolledtoalargeextentbytran-scriptionfactors(TF).Theseregulatoryproteins,whichoperateinthenucleus,havetheabilitytoselectivelybindpromoterregionsinspecificgenestoinfluencetheleveloftheirexpression.Byincreasingordecreasingtranscriptionoftheirtargetgenes,theycanhaveaprofoundeffectonthebiologicalpro-cessesthesegenescontrol(Latchman2003).Inthecaseofmetabolism,theycaninfluencetheexpressionofpathwaygenesandultimatelyaffectmetabolicflux.Transcriptionfactorsarealsoinvolvedin

controllingmanyplantdevelopmentalprocesses,inparticularmanyofthedifferentiationeventsleadingtometabolicallyspecializedcelltypes(Broun2004,2005).Theroleoftranscriptionfactorsincontrollingmetabolicfluxanddifferentiationofthecellularstructureswhereterpenoidsareproducedishigh-lightedinthisreview.Wearealsodescribingsomeofthenovelapproachesthataimatidentifyingspecifictranscriptionfactorsinvolvedinthecontrolofplantterpenoidproduction,eitherthroughtheirdirectinvolvementwiththepathway,orthroughtheirmodulationofcellulardifferentiationprocessesrele-vanttometaboliteaccumulation.

Transcriptionfactorsandtheregulationoffluxthroughpathwaysofsecondarymetabolisminplants:exampleoftheflavonoidpathway

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名词简答整理

名词简答整理

增强子：是指能使与它连锁的基因转录频率明显增加的DNA序列。

它可以在启动子的上游，也可以在启动子的下游，绝大多数增强子具有组织特异性。

Operon：是细菌基因表达调控的一个完整单元，包含结构基因以及能够被调节基因产物所识别并结合的顺式作用元件。

朊病毒：是一种无免疫原性但能在细胞内复制、并能侵染动物的疏水性蛋白质。

致病途径具有自发性、遗传性和传染性三个特征。

C值矛盾：生物体进化程度高低与大C值不成明显相关（非线性）；亲缘关系相近的生物大C值相差较大；一种生物内大C值与小c值相差极大。

RNAi：是由外源双链RNA产生的21~25nt小的干涉RNA而触发内生同源mRNA降解的过程，是一种转录后水平上的基因沉默机制。

RNA编辑：RNA编辑是指由RNA水平的核苷酸改变所引起的密码子发生变化的一种预定修饰，一种RNA编辑是以另一RNA为模板来修饰mRNA前体。

通过编辑，可以给mRNA前体添加新的遗传信息。

移码突变：由于缺失或插入而导致突变位点以后的三联体密码可读矿改变。

Transcription：是指以DNA为模板，在依赖于DNA的RNA聚合酶的催化下，以4种NTP（A TP、CTP、GTP和UTP）为原料，合成RNA的过程。

顺式作用元件：是指DNA上对基因表达有调节活性的某些特定的调控序列，其活性仅影响与其自身处于同一DNA分子上的基因。

分子伴侣：是结合其他不稳定蛋白质并稳定其构象的一类蛋白质。

通过与部分折叠的多肽协调性地结合与释放，分子伴侣促进了包括蛋白质折叠、寡聚体装配、亚细胞定位和蛋白质降解等多个过程。

转座子：是染色体或质粒上的一段独立的DNA序列，作为一个可以重组但不交换的遗传单元，能在原位保留其本身的情况下，从一个位点转移到另一个位点。

DNA复杂度：是DNA分子中无重复的核苷酸序列的最大长度。

负调控：阻遏蛋白结合在操作子位点，阻止基因的表达。

没有调节蛋白时操纵元内结构基因是表达的，而加入调节蛋白后结构基因的表达活性被关闭，这种调节称为负调节。

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6
1. Extracellular signal molecules: Ligand/Agonist are normally released by signal-producing cells, reach and bind to the receptor protein of target cells.
most water-soluble molecules/factors bind to cell membrane receptors and activate the signaling transduction pathway.
13
Signaling pathway via nuclear receptor
Signal Transduction Pathways & the Clinical Implications
1
CONTENT
1. Overview: Concept, components, common features of cell signal transduction pathways
5
Signal molecules
Ligand/Agonist
Proteins and peptides:
Hormones, cytokines
Bind to Amino acid derivatives: membrane Catecholamine receptors
Chemical Signal
Motility
Death Transformation
Cell signaling affects virtually EVERY ASPECT of cell structures and functions. 4
酵母双杂交原理与实验具体流程.

酵母双杂交原理与实验具体流程.


图2romoters and other cis-acting regulatory elements play a crucial role in yeast-based expression systems and transcriptional assays such as the MATCHMAKER One- and Two-Hybrid Systems. Differences in the promoter region of reporter gene constructs can significantly affect their ability to respond to the DNA-binding domain of specific transcriptional activators; promoter constructs also affect the level of background (or leakiness) of gene expression and the level of induced expression. Furthermore, differences in cloning vector promoters determine the level of protein expression and, in some cases, confer the ability to be regulated by a nutrient (such as g al actose in the case of the G AL 1p romoter) .
酵母双杂交系统原理及具体 操作流程
酵母双杂交系统可进行两个蛋白互作分析，可用
一个已知的蛋白因子（在双杂交系统中称为诱饵蛋白）
促红细胞生成素的表达调控机制及其在慢性病贫血治疗中的应用

促红细胞生成素的表达调控机制及其在慢性病贫血治疗中的应用

促红细胞生成素的表达调控机制及其在慢性病贫血治疗中的应用孙士鹏;刘贵建【摘要】促红细胞生成素（EPO）为165个氨基酸残基组成的糖蛋白，主要由胎肝和成人肾皮质的成纤维细胞生成。

EPO的表达受到多种转录因子和表观遗传学调控。

EPO与其受体结合后主要通过激活Jak2／stat5通路，进而激活 Pim、c-Myc、OncostatinM、Bcl-2、Bcl-xL、SOCS 和 D-type cyclin 等基因，在红细胞生成过程中起到抗细胞凋亡和促进细胞增殖等重要作用。

使用促红细胞生成剂上调血红蛋白含量，进而改善贫血患者的能量水平和生活质量具有重要意义，但长期使用存在一些副作用。

本文对EPO表达调控机制及其在贫血治疗中的应用进行论述。

%Erythropoietin (EPO) is a glycoprotein composed of 165 amino acid residue that is mainly produced in the fetal liver and adult kidney cortex fibroblast. The binding of EPO and its receptor can activate Jak2/stat5 pathway. Several important Stat5 target genes, such as Pim, c-Myc, OncostatinM, Bcl-xL SOCS or D-type cyclins are required for functional erythropoiesis. The expression of EPO is regulated by a variety of transcription factors and epigenetic regulation. Erythropoiesis-stimulating agents (ESA) can increase hemoglobin levels, and thus improve the energy level and quality of life in patients with anemia, but the long-term use of ESA also has some side effects. In this paper, the EPO expression regulation mechanism and its application in the treatment of anemia of chronic disease is discussed.【期刊名称】《分子诊断与治疗杂志》【年(卷),期】2014(000)006【总页数】5页(P424-428)【关键词】促红细胞生成素;缺氧;甲基化;贫血【作者】孙士鹏;刘贵建【作者单位】中国中医科学院广安门医院检验科，北京 100053;中国中医科学院广安门医院检验科，北京 100053【正文语种】中文1906年在激素能够通过血液运送到体内较远的组织器官发挥功能的新观点影响下，法国学者Carnot和DeFlandre提出缺氧条件下红细胞生成受到一种激素调控，这种激素命名为促红细胞生成素（erythropoietin，EPO）［1］。