清华大学：《分子生物学》（英文版）Chapter 21 Regulation of Transcription

Chapter 21 Regulation of Transcription 莘大

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. 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. 1 8 Insulators block enhancer actions 21 19 Insulators can vary in strength 21.20 A domain has several types of elements 21.2 1 Gene expression is associated with demethylation 22 CpG islands are regulatory targets 消当

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

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

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 APl erum SRE CCATATTAGG SRE Table 21. 1 Incucible transcription factors bind to response elements that identify groups of promoters or enhancers subject to coordinate control 请莘大

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 MRBRE BLETRE MREGC MRE TATA 260-240-220200-180-160140120-100305040-200 Steroid- receptor AP 2 2(21 ?sP1? Protein 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. 请莘大

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

nactive Cond ition 21. 3 There are many Protein synthesized No protein Homeoproteins types of DNA-binding Protein phosphorylated domains A HSTF Inactive prots Protein de phosphorylated Figure 2 1.2 The activity of a Inactive protein Ligand binding regulatory transcription 八 factor may be controlled by receptors Inactive prot: synthesis of protein. Cleavage to release active factor covalent modification of 八N protein, ligand binding, or Membran Releas inhibitor binding of inhibitors that 八A sequester the protein or Inactive prot NFk日 affect its ability to bind to nhi bitor DNA 八A 消当 I nactive part

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 facto many types of DNA Jun Fos p65-p50 dimer binding domains NF↓B 八AAA AP-1 may b regulated by Phosphorylation of ↓m ↓ Figure 28.19 Oncogenes - kB releases NF-k日 that code for transcription factors have mutations that Inactivate transcription Function of oncogenic factor (v-erbA and possibly v-o V-Rel has lost regions needed to stay in cytoplasm rel) or that activate transcription(v-jun and vvv wvoy V-IOS v-Rel may prevent p65/p50 fom v-Jun and v-Fos may activate target v-ErbA cannot activate orming dimer andor activating genes without responding to usual transcription, and also inhibits transcription 消当

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 o呀pQ zn t+ oo②o Figure 21.3 Transcription factor SPl has a series of three zinc fingers, each with a characteristic pattern of cysteine and histidine residues that constitute the zinc-binding site 请莘大

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 0● Figure 21. 4 Zinc ● fingers may form OoO a-helices that Forms Forms B-sheeto-hellx insert into the major groove associated withβ sheets on the other side 请莘大

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 4A zinc finger motif is a ○ ● ○ DNA-binding domain ooO +自 90000 OO 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 the first finger shows that ■■■■■■ discrimination between GRE and Glucocorticoid Estrogen ERE target sequences rests on specificity spec ificity two amino acids at the base Same sequence in both receptors lO Different sequence in each receptor 请莘大

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