清华大学：《分子生物学》课程PPT教学课件（基因ene）第二十一章 转录的调控（Regulation of Transcription）

Chapter 21 Regulation of Transcription 清革大当

Chapter 21 Regulation of Transcription

21.1 Introduction 21.2 Response elements identify genes under common regulation 21.3 There are many types of DNA-binding domains 21.4 A zinc finger motif is a DNA-binding domain 21.5 Steroid receptors are transcription factors 21.6 Steroid receptors have zinc fingers 21.7 Binding to the response element is activated by ligand-binding 21.8 Steroid receptors recognize response elements by a combinatorial code 21.9 Homeodomains bind related targets in DNA 21.10 Helix-loop-helix proteins interact by combinatorial association 21.11 Leucine zippers are involved in dimer formation 21.12 Transcription initiation requires changes in chromatin structure 21.13 Chromatin remodeling is an active process 21.14 Activation of transcription requires changes in nucleosome organization at the promoter 21.15 Histone acetylation and deacetylation control chromatin activity 21.16 Polycomb and trithorax are antagonistic repressors and activators 21.17 An LCR may control a domain 21.18 Insulators block enhancer actions 21.19 Insulators can vary in strength 21.20 A domain has several types of elements 21.21 Gene expression is associated with demethylation 21.22 CpG islands are regulatory targets 情莘大当

21.1 Introduction 21.2 Response elements identify genes under common regulation 21.3 There are many types of DNA-binding domains 21.4 A zinc finger motif is a DNA-binding domain 21.5 Steroid receptors are transcription factors 21.6 Steroid receptors have zinc fingers 21.7 Binding to the response element is activated by ligand-binding 21.8 Steroid receptors recognize response elements by a combinatorial code 21.9 Homeodomains bind related targets in DNA 21.10 Helix-loop-helix proteins interact by combinatorial association 21.11 Leucine zippers are involved in dimer formation 21.12 Transcription initiation requires changes in chromatin structure 21.13 Chromatin remodeling is an active process 21.14 Activation of transcription requires changes in nucleosome organization at the promoter 21.15 Histone acetylation and deacetylation control chromatin activity 21.16 Polycomb and trithorax are antagonistic repressors and activators 21.17 An LCR may control a domain 21.18 Insulators block enhancer actions 21.19 Insulators can vary in strength 21.20 A domain has several types of elements 21.21 Gene expression is associated with demethylation 21.22 CpG islands are regulatory targets

21.1 Introduction Activation of gene structure Initiation of transcription Processing the transcript Transport to cytoplasm Translation of mRNA 清菜大当

Activation of gene structure Initiation of transcription Processing the transcript Transport to cytoplasm Translation of mRNA 21.1 Introduction

21.2 Response elements identify genes under common regulation Regulatory Agent Module Consensus Factor Heat shock HSE CNNGAANNTCCNNG HSTF Glucocorticoid GRE TGGTACAAATGTTCT Receptor Phorbol ester TRE TGACTCA AP1 Serum SRE CCATATTAGG SRF Table 21.1 Incucible transcription factors bind to response elements that identify groups of promoters or enhancers subject to coordinate control. 情華大当

Table 21.1 Incucible transcription factors bind to response elements that identify groups of promoters or enhancers subject to coordinate control. 21.2 Response elements identify genes under common regulation Regulatory Agent Module Consensus Factor Heat shock HSE CNNGAANNTCCNNG HSTF Glucocorticoid GRE TGGTACAAATGTTCT Receptor Phorbol ester TRE TGACTCA AP1 Serum SRE CCATATTAGG SRF

21.2 Response elements identify genes under common regulation Response elements GRE BLE MRRE BLETRE MREC MRE TATA 激 ■ -260 -240 -220 -200 -180-160-140 -120 -1008060 40-20 0 Steroid- receptor AP 2 P rotein binding Figure 21.1 The regulatory region of a human metallothionein gene contains regulator elements in both its promoter and enhancer.The promoter has elements for metal induction;an enhancer has an element for response to glucocorticoid.Promoter elements are shown above the map,and proteins that bind them are indicated below. 清菜大当

Figure 21.1 The regulatory region of a human metallothionein gene contains regulator elements in both its promoter and enhancer. The promoter has elements for metal induction; an enhancer has an element for response to glucocorticoid. Promoter elements are shown above the map, and proteins that bind them are indicated below. 21.2 Response elements identify genes under common regulation

Inadive Condition Active Condition Example 21.3 There are many Protein synthesized types of DNA-binding No protein 中 Homeoproteins Protein phosphorylated domains 八风凡 八NN八N HSTF Inactive prot Protein dephosphoryated NN个 八八八N入 Figure 21.2 The activity of a Inactive protein Ligand binding regulatory transcription 八MN八八N ny factor may be controlled by Inactive prot synthesis of protein, Cleavage to release adive factor covalent modification of 八凡八八N 八入八代风 Sterol protein,ligand binding,or response Membrane-bound protein Release byinhibitor binding of inhibitors that NM八八八N 八八N sequester the protein or Inactive prot NF-kB affect its ability to bind to Inhibitor Change of partner DNA. 八NNN Inactive prot → 品DAD) 情菜大当 Inactive partner

Figure 21.2 The activity of a regulatory transcription factor may be controlled by synthesis of protein, covalent modification of protein, ligand binding, or binding of inhibitors that sequester the protein or affect its ability to bind to DNA. 21.3 There are many types of DNA-binding domains

21.3 There are Mechanism of factor many types of DNA- 1-k8 Jun Fos p65-p50 dimer binding domains NFk短 风风入入N N八NM风MW AP-1 may be Ligand binding acivates thyroid hormone receptor requlated by (as dimer with RXR) Phosphorylation of phosphorylation -kB releases NF-k日 Figure 28.19 Oncogenes As that code for transcription factors have mutations that VV inactivate transcription Function of oncogenic factor (v-erbA and possibly v- v-Rel has lost regions needed to stay in cytoplasm V-E rbA has lo过 v-Jun y-Fos have temminal TH-pinding ate rel)or that activate truncations and point mutations 八NNN transcription (v-jun and M八八N v-fos). v-Rel may prevent p65/p50 fom y-Jun and v-Fos may activate target v-ErbA cannot activate forming dimer and/or adtivating genes without responding to usual transcription,and also inhibits transcription controls 清菜大兰

Figure 28.19 Oncogenes that code for transcription factors have mutations that inactivate transcription (v-erbA and possibly v￾rel) or that activate transcription (v-jun and v-fos). 21.3 There are many types of DNA￾binding domains

21.4 A zinc finger motif is a DNA-binding domain Figure 21.3 Transcription factor SPI has a series of three zinc fingers,each with a characteristic pattern of cysteine and histidine residues that constitute the zinc-binding site 清菜大当

Figure 21.3 Transcription factor SP1 has a series of three zinc fingers, each with a characteristic pattern of cysteine and histidine residues that constitute the zinc-binding site. 21.4 A zinc finger motif is a DNA-binding domain

21.4 A zinc finger motif is a DNA-binding domain Figure 21.4 Zinc 000 fingers may form a-helices that Foms Forms B-sheeto-helix insert into the major groove, associated with B- sheets on the other side. 清第大当

Figure 21.4 Zinc fingers may form a-helices that insert into the major groove, associated with b￾sheets on the other side. 21.4 A zinc finger motif is a DNA-binding domain

21.4 A zinc finger motif is a 0 DNA-binding domain 8 8 9000000 0000 Figure 21.5 The first finger of a DNA binding Dimerization steroid receptor controls specificity of DNA-binding (positions shown in red);the second finger controls specificity of dimerization(positions shown in blue).The expanded view of 8 the first finger shows that 090.。 discrimination between GRE and 6@→@ Glucocorticoid Estrogen ERE target sequences rests on specificity specificity two amino acids at the base. Same sequence in both receptors Different sequence in each receptor 情華大当

Figure 21.5 The first finger of a steroid receptor controls specificity of DNA-binding (positions shown in red); the second finger controls specificity of dimerization (positions shown in blue). The expanded view of the first finger shows that discrimination between GRE and ERE target sequences rests on two amino acids at the base. 21.4 A zinc finger motif is a DNA-binding domain