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1、Chapter 7 / 第7章,Regulation of Gene Expression in eukaryotes 7.1 Histones and Transcriptional Regulation 7.2 Post-Transcriptional Regulation 7.3 Nuclear Export 7.4 RNA stability 7.5 Translational control 7.6 mRNA localization 7.7 Protein regulation 7.8 Experiments,真核生物基因表达调控 7.1 组蛋白与转录调控 7.2 转录后调控 7.
2、3 细胞核输出 7.4 RNA稳定性 7.5 翻译调控 7.6 mRNA定位 7.7 蛋白质调控 7.8 实验研究,Same DNA, different cells 相同的DNA、不同的细胞,Neural cells 神经细胞,Blood cells 血液细胞,A muscle cell 肌肉细胞,Human cells 人体细胞,We are going to learn ,7.1 Histones and Transcriptional Regulation,Homeodomain 同源异型域,Leucine zipper 亮氨酸拉链,Zinc finger 锌指,HLH 螺旋-环-螺旋
3、,Histones / 组蛋白,?,Chapter 2,7.1.1 Histones and DNA organization 组蛋白与DNA组织,核心组蛋白,八聚体,Histones contain many amino acids with positive charges 组蛋白含有许多带正电荷的氨基酸,His / Lys / Arg,+,+,+,+,+,+,+,+,+,+,+,+,Nucleosome / 核小体,The Beads-on-a-string model 线 珠 模 型, 60 bp, 150 bp,The 30nm fibre / 30nm纤维,Levels of DN
4、A organization DNA组织的水平,Now showing Chromosome Packing,File: biophoto7 Lehninger Principles of Biochemistry Three dimensional packing of nuclear chromosome (5),Euchromatin and heterochromatin常染色质 和 异染色质,7.1.2 Histones and Transcription 组蛋白与转录,Structure of histones / 组蛋白的结构,Histone tail,7.1.3 Covalen
5、t modification of histones 组蛋白的共价修饰,Acetylation / 乙酰化作用,CH3 ,CH3,CH3,Histone code / 组蛋白密码,K9,K4,K9,K4,Repression,K9,K4,CH3,Activation,Histone code / 组蛋白密码,K14,K8,H10,K8,H10,K14,H10,K14,K8,Effect,Effect,Effect,Histone code / 组蛋白密码,H10,K14,K8,Effect,A coded lock（密码锁）,7.1.4 Proteins that recognize and
6、modify histones 识别和修饰组蛋白的蛋白质,Chromatin remodeling protein,Swi/Snf complex,Specific transcription factors attract various enzymes 特异转录因子吸引不同的酶,Reference: Karpusas M, Nolte M, Benton CB, Meier W, Lipscomb WN, Goelz S The crystal structure of human interferon beta at 2.2-A resolution Proc. Natl. Acad.
7、Sci. U. S. A. v94, p.11813-11818Description: Human Interferon-Beta Crystal Structure. Deposition: 1997/9/9 Author:Karpusas M, Nolte M, LipscombWTaxonomy: Homo sapiensMMDB: 8039 PDB: 1AU1 Structure Neighbors: VAST,INF-,Regulation of INF- gene (1/3),INF- gene,Regulation of INF- gene (2/3),Regulation o
8、f INF- gene (3/3),7.2 Post-Transcriptional Regulation 转录后调控,Chapter 5,Sex determination of fruit flies 果蝇的性别决定,Alternative splicing of the Sxl gene,Alternative splicing of the Sxl gene,Further studying,R. F. Weaver, Molecular Biology, Chapter 14,Alternative polyadenylation / 可变聚腺苷化,7.3 Nuclear Expor
9、t / 细胞核输出,Export of heat shock protein mRNAs 热休克蛋白mRNA的输出,Yeast cells www.zeiss.de/C12567BE0045ACF1/ContentsWWWInte,HIV: human immunodeficeincy virus,HIV,Export of HIV mRNAs / HIV mRNA的输出,7.4 RNA stability / RNA稳定性,Common mechanism for mRNA degradation,7.4.1 mRNA Stability Regulation by Proteins 蛋白质
10、调控mRNA稳定性,ARE: AU-rich element,UTR: untranslated region,Function of Protein TTP,Growth signal,TTP: a CCCH zinc finger protein,Transferrin / 运铁蛋白,www.umassd.edu/cas/chemistry/guo/guoresearch.html,Membrane coated vesicle,Fe3+,Fe3+,Endosome pH 5.0,Fe3+,Fe3+,pH triggers Fe3+ release,Transferrin cycle,Fe
11、3+,Fe3+,pH 7.4,Transferrin receptors,Diferric transferrin,Cytosol,Regulation of transferrin by aconitase 顺乌头酸酶对运铁蛋白的调控,7.4.2 mRNA Stability Regulation by Small RNAs 小RNA调控mRNA稳定性,RNA stability,Regulated by proteins,Regulated by small RNAs,miRNA siRNA,RNA interference (RNAi, RNA干涉),RNA interference:
12、A process that uses siRNA or miRNA to induce degradation of a target mRNA. （一种siRNA或miRNA诱导目标mRNA降解的过程）,www.english.vietnamnet.vn/./2006/10/618962/,Two U.S. scientists won Nobel Prize in medicine (October 4, 2006) U.S. scientists Andrew Fire and Craig Mello won the Nobel Prize in physiology or medic
13、ine Monday for discovering a powerful way to turn off the effect of specific genes, opening potential new paths for disease treatment.,Functions of siRNA and miRNA (1/3),Functions of siRNA and miRNA (2/3),Functions of siRNA and miRNA (3/3),RISC: RNAi Silencing Complex RNAi沉默复合体, RISC 1U04.val,Origin
14、 and function of miRNA,Origin and function of siRNA,7.5 Translational control / 翻译调控,7.5.1 Global Control / 全局控制,www.uniklinikum-giessen.de/./res_ires.htm,Picornavirus 小核糖核酸病毒,Chapter 6,Global control through phosphorylation,Normal cycle at translation initiation,Global control through 4E-BP,Global
15、control through 4E-BP,7.5.2 mRNA-Specific Control mRNA特异性控制,mRNA with CPE,CPE: Cytoplasmic Polyadenylation Element （细胞质聚腺苷酸化元件）, Maskin and eIF4E,Ferritin / 铁蛋白,Crystal Structure Of Ferritin (Tm1128) From Thermotoga Maritima,File: Ferritin 1VLG.val,Fe,Regulation of ferritin by aconitase 顺乌头酸酶对铁蛋白的调控,7.6 mRNA localization / mRNA定位,Many proteins have no signals,Many proteins contain signals that cause them to localize to specific areas after translation. However, many other proteins do not contain such signals. Their localization depends to a great extent on wher
