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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
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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 7.3 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 A muscle cell 肌肉细胞 Blood cells 血液细胞 Human cells 人体细胞
7.1 Histones and Transcriptional Regulation Zinc finger锌指 Homeodomain 同源异型域 HLH 螺旋-环-螺旋 Leucine zipper 亮氨酸拉链
Histones / 组蛋白 ? Chapter 2
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
The Beads-on-a-string model线 珠 模 型 ~ 60 bp ~ 150 bp
Structure of histones / 组蛋白的结构 Histone tail
7.1.3 Covalent modification of histones组蛋白的共价修饰
Histone code / 组蛋白密码 K4 K4 CH3 — K4 —CH3 —CH3 K9 K9 —CH3 K9 Repression Activation
Histone code / 组蛋白密码 — — — — — Ac P Ac P P K8 K8 K8 H10 H10 H10 K14 K14 K14 Effect Effect Effect
Histone code / 组蛋白密码 — — P Ac K8 H10 K14 Effect A coded lock(密码锁)
7.1.4 Proteins that recognize and modify histones识别和修饰组蛋白的蛋白质 Chromatin remodeling protein
Specific transcription factors attract various enzymes特异转录因子吸引不同的酶 INF-β Reference: Karpusas M, Nolte M, Benton CB, Meier W, Lipscomb WN, Goelz S The crystal structure of human interferon beta at 2.2-A resolutionProc. Natl. Acad. 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
Regulation of INF-β gene (1/3) INF-β gene
Regulation of INF-β gene (2/3) “There is not enough room for me. Please help to push away the histones.”
Regulation of INF-β gene (3/3) “Thank you. I got it”
7.2 Post-Transcriptional Regulation转录后调控 Chapter 5
Further studying R. F. Weaver, Molecular Biology, Chapter 14
Export of heat shock protein mRNAs热休克蛋白mRNA的输出 Yeast cellswww.zeiss.de/C12567BE0045ACF1/ContentsWWWInte
7.4.1 mRNA Stability Regulationby Proteins蛋白质调控mRNA稳定性 UTR: untranslated region ARE: AU-rich element
Function of Protein TTP Growth signal TTP: a CCCH zinc finger protein
Transferrin / 运铁蛋白 Transferrin receptors pH ~7.4 Diferric transferrin Fe3+ Fe3+ Membrane coated vesicle Endosome pH ~5.0 Fe3+ Fe3+ Fe3+ Fe3+ pH triggers Fe3+ release Cytosol Transferrin cycle www.umassd.edu/cas/chemistry/guo/guoresearch.html
Regulation of transferrin by aconitase顺乌头酸酶对运铁蛋白的调控
7.4.2 mRNA Stability Regulationby Small RNAs小RNA调控mRNA稳定性 RNA stability Regulated by small RNAs Regulated by proteins miRNA siRNA
RNAinterference (RNAi,RNA干涉) RNA interference: 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) 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 medicine Monday for discovering a powerful way to turn off the effect of specific genes, opening potential new paths for disease treatment. www.english.vietnamnet.vn/.../2006/10/618962/
RISC: RNAiSilencing ComplexRNAi沉默复合体 www.abcam.com/index.html File: RISC 1U04.val