Gene expression regulation ***Enmin Li

Section 1** Basic concept, specificity and modality of gene expression Section 2** Basic principle of gene expression regulationSection 3** Regulation of gene expression in prokaryote Section 4** Regulation of gene expression in eukaryote

Section 1

The basic concept, specificity and modality of gene expression

1.1 The concept of gene expression gene expressiontranscriptiontranslation = +

DNAs RNAs Proteins1 proteins2 RNAs1 proteins2 RNAsInteraction among large biomolecules

1.2 The specificity of gene expression in the time and the space

1.2.1 The temporal specificity of gene expression The temporal specificity is that some specific genes in genome are expressed in order of specific timeThe temporal specificity is also stage specifi-city in the polycellular biosomes The expressed genes in early developmental steps are more than in other steps in polycellular biosomesThe expressed genes relate with biological function.

1.2.2 The spatial specificity of gene expression In the polycellular biosomes the spatial speci- ficity of gene expression is that one or some specific genes in the genome are expressed in different systems, organs, tissues and cells in order of space.The spatial specificity of gene expression is also known as tissue specificity or cell specificity.The expressed genes relate with biological function.

1.3.1 constitutive gene expression Some genes in genome are known as housekeeping genes. The expression of housekeeping genes in genome are also called constitutive gene expression. Constitutive gene expression is continual in most cells.

The expressive products of constitutive genes are absolutely necessary in all over life process. The expression of constitutive genes are less effected by environment factors. The constitutive gene expression are only effected by interacting between promoter and RNA polymerase.

1.3.2 Inductive and repressive gene expression The expression of some genes in genome are more effected by environment factors. The increase of gene expression which is effected by environment factors are called induction, in contrast, the decrease of that are repression.

The expression of induced or repressed genes are regulated by other factors, besides interaction between promoter and RNA polymerase. The special elements are located in the regulation region of induced or repressed genes. Induction and repression of gene expression correspond with each other.

1.4 Biological significance of gene expression regulation acclimation keep growth and proliferation keep individual development and differentiation

Section 2 Basic principle of gene expressionregulation

2.1 multilevel regulation of gene expressioncheck point activity of gene structure in genome DNA amplification DNA rearangement DNA methylation initiation of RNA transcription* process of RNA post-transcription transport of RNA post-process initiation of protein translation process of protein post-translation

2.2.1.2 the prokaryotic operon The concept of the operon was first proposed in 1961 by Jacob and Monod. An operon is a whole unit of prokaryotic gene expression which includes a set of structural genes and its promoter, operator and other control elements which are recognized and bond by regulatory gene products.

2.2.1.3 Other regulator of prokaryotic operons special DNA sequence in some prokaryotic operons can bind with activator of RNA polymerase increase transcription of operons mediate positive regulation of operons The positive regulation is not main mechanism about gene expression regulation of operons, but the negative regulation is .

2.2.1.4 cis-acting elements of eukaryotic gene The cis-acting elements are DNA fragments. The cis-acting elements are the regulator of eukaryotic gene transcription There are cis-acting elements in the flakings or the introns of eukaryotic gene. The cis-acting elements include promoter,enhancer, silencer and so on.

2.2.2 regulation protein 2.2.2.1 regulation protein of prokaryotic genes specific factors decide identification and bind between RNA polymerase and specific promoter repressor bind operator and repress gene transcription activator: bind a special DNA sequence next to promoter advance to bind between RNA polymerase and promoter and to form transcription initiation complex.

2.2.2.2 regulation protein of eukaryotic genes transcription factor, it is also trans-acting factor. cis-acting proteinPBBPAAprotein A trans-acting proteintrans-acting factorprotein B cis-acting proteintrans-regulationcis-regulation

2.2.3 RNA polymerase

2.2.3.1 promoter of prokaryotes/eukaryotes effect on RNA polymerase The promoter of prokaryotes/eukaryotes is consist of transcription initiation site, RNA polymerase identification and binding site and other regulation elements. The promoter of eukaryotes is more complicated than that of prokaryotes.

The sequence of different promoter is certain different. The affinity of prokaryotic promoter with RNA polymerase effects directly on frequency of gene transcription initiation The affinity between eukaryotic RNA polymerase and promoter is less, when RNA polymerase is single. The eukaryotic RNA polymerase can bind with promoter after forming complex with basic transcription factor.

2.2.3.2 regulation proteins effect on activity of RNA polymerase Specific promoter decides basic transcription frequency of genes. The regulation proteins can change transcription frequency of genes. The conformation or the expression level in the cell of regulation proteins gets a change under stimulation of environment signal.

2.2.4 DNA-protein and protein-protein interaction in transcription regulation of eukaryotic genes2.2.4.1 DNA-protein interaction

Identification and bind between cis-acting proteins or trans-acting factors and cis-acting elements Its interaction is a non-covalent bond. Form DNA-protein complex finally

2.2.4.2 protein-protein interaction The most regulation protein can form homodimer, heterodimer, homopolymer or heteropolymer before binding with cis-acting element. Ability of some regulation protein to bind with its cis-acting element is increased or decreased after polymerization. Some regulation protein dont bind with DNA, but can effect the activity binding between DNA and other regulation protein by protein-protein interaction.

Section 3 Regulation of prokaryotic gene expression3.1 Characters of transcribed regulation in prokaryotic genes3.2 Regulation of transcribed initiation in prokaryotic genes3.3 Regulation of transcribed termination in prokaryotic genes3.4 Regulation of proteic translation in prokaryote

3.1 characters of transcriptional regulation in prokaryotic genes 3.1.1 The function of factors The factors bind a special element in 5 flaking region of genes in the stage of transcribed initiationThe factors decide the specificity of transcribed genesThe factors mediate holoenzyme of RNA polymerase binding to specific promoter of genesDifferent factors decide transcription of different genes.

3.1.2 universality of operon model the most prokaryotic genes There are many operons in order in prokaryotic genome. Dont discover operon in eukaryotic genome.3.1.3 universality of repression mechanism The repression mechanism is the main mechanism of transcriptional regulation of prokaryotic genes

3.2 regulation of transcribed initiation in prokaryotic genes

The negative regulation mechanism of the repressor cooperate with the positive regulation mechanism of the CAP control gene transcription of lac operon by kind and concentration of carbohydrate from the environment.

3.3 regulation of transcribed termination in prokaryotic genes

3.3.3 attenuation regulation mechanism of gene transcription of trp operon in E.coli

3.4 regulation of proteic translation in prokaryote

3.4.1 autoregulation/autogenous control ProteinmRNADNA same mRNA53started region

Antisens RNA

Section 4 Regulation of eukaryotic gene expression4.1 character of eukaryotic genomic structure4.2 character of expressional regulation of eukaryotic genes4.3 regulation of transcription for RNA pol I and RNA pol III4.4 regulation of transcriptional initiation for RNA pol II4.5 regulation of transcriptional termination for RNA pol II4.6 regulation of past-transcription for RNA4.7 regulation of translation for protein

4.1 Character of eukaryotic genomic structureThe eukaryotic genome is very great.The structure of eukaryotic genome is very complex.There is only a gene in a transcriptional unit of eukaryotic genome.There are a lot of repeat sequences in eukaryotic genome.Gene are discontinuous, there are noncoding sequences in the most eukaryotic gene.

The histons in active gene region change often as follows: The histons is prone to be modified, in result its structure becomes instability.The dimer H2A-H2B is prone to be replaced out from nucleosome.The instability of dimer H2A-H2B is increased.The rich-Lys H1-like histons are decreased.

4.2.3 The positive regulation is main in gene transcription regulation of eukaryotesThe most transcriptional regulation proteins are transcription activation proteins.The affinity between RNA polymerase and promoter in eukaryotes is very weaker or not. RNA polymerase must depend on one or many activation proteins to bind with promoter. The positive regulation is universality in gene transcription regulation of eukaryotes.

The eukaryotic genome is very great.There are many cis-acting elements in a gene regulation region, in result that specificity of interaction between activation protein and DNA is increased.Many activation proteins regulate a gene, therefore the regulation efficiency is higher.A activation proteins regulate many gene, therefore the regulation is more economical.

4.2.4 The transcription and the translation are separated in different area , this is prone to regulate exactly in gene transcription4.2.5 The process of post-transcription modification is more complex and perfect, therefore links of gene expression regulation is increased.

4.3 regulation of transcription for RNA pol and RNA pol

4.4 regulation of transcriptional initiation for RNA pol

4.4.1 cis-acting elementaccording to function, main includingpromoter, enhancer, silencer and so on

4.4.1.1 promoterIt is consist of RNA polymerase binding site, a set of other functional elements which control transcription and a transcription initiation site at least. The length of every functional elements in the promoter is about 7-20 bp.Promoter sequence of different genes is a little different.Most gene promoter sequence have TATA box.

TATA box is the most basic and important functional element in the promoter.The consensus sequence of TATA box is TATAAAA locating in -25 -30 bp region of transcription start site upstream.TATA box controls veracity and frequency of gene transcription.GC boxGGGCGGand CAAT box GCCAATis more frequent in the promoter.GC box and CAAT box locate in -30 -110 bp region of transcription start site upstream.

The promoter locates in upstream of coding region of the gene certainly.The promoter has strict direction.The most simple promoter is consist of TATA box and transcription start site, but the typical promoter often contains also GC box and/or CAAT box in upstream of TATA box.

The promoter of some genes dont contain TATA box.The promoter without TATA box always contains many transcription start sites, and contains rich-GC sometimes.The gene that contains the promoter without TATA box is house keeping gene or the gene which plays a role in fetation, tissue differentiation, tissue damage regeneration and so on.

The role of the enhancer dont relate with its distance from transcription start site. The enhancer is very far from gene transcription start site(1~30/50kb) and locates not only in genic upstream, but also in genic downstream, sometimes in the intron. Some important functional elementsfor example core DNA sequence which is bond with special transcription factors, is in the enhancer and the promoter at same time. TATA boxEnhencer-1-200Enhancer-3+10kb to +50kbEnhancer-2-10kb to -50kbGeneregulatoryproteinsGeneregulatoryproteinsgene53RNA pol IItranscriptioninitiation complex

4.4.1.3 silencer The silencers are the negative elements in gene transcription regulation, in contrast to the enhancers. The gene transcription is suppressed when specific regulation protein have bound with the silencers.Some silencers play the role of enhancers sometime this mainly depends to the character of regulation proteins in the nucleus.

4.4.2 transcription regulation factorsThe transcription regulation factors are also called transcription factors (TF).Most transcription regulation factors are trans-acting factors, a few ones are cis-acting proteins.

4.4.2.1 type of transcription factors4.4.2.1.1 general transcription factorsIt is necessary for the RNA polymerase bind with the promoter. It decides RNA transcription type .It is also regarded as a component of RNA polymerase.

4.4.2.1.2 special transcription factorsIt is necessary for individual gene transcription.It decided the specificity of gene transcription in the time and the space. Most special transcription factors are transcription activators, a few ones are transcription inhibitors.

Most transcription activators are the proteins binding with the enhancer.Most transcription inhibitors are the proteins binding with the silencer.Some transcription inhibitors dont directly interact with DNA, but bind with the general transcription factor II-D or some transcription activators and decrease effective concentration of the latter in cell and suppress gene transcription.

4.4.2.2 structure of transcription factorUsually, a transcription factor contains a DNA binding domain and a transcription activation domain.Many transcription factors also contain a domain which mediate protein-protein interaction, for example dimerization domain.

4.4.2.2.1 DNA binding domain It is consist of 60~ 100 amino acid residues usually. the most familiar structures: zinc finger structure basic - helix structure other structures: basic leucine zipper structurebZIP basic helix-turn helix structurebHTH basic helix-loop-helix structurebHLH

basic - helix domain(bAH)DNA binding domain of CTF1 (transcription factor)

4.4.2.2.2 transcription activation domain It is usually consist of 30100 amino acid residues . It is divided three types as follows: acidic activation domain glutamine-rich domain proline-rich domain

4.4.2.2.3 dimerization domain It is the basic leucine zipper or basic helix loop helix in protein structure.

TF II E

1 A DNAB tRNAC mRNAD rRNAE F hnRNA

2 A B C D E

3 A IB ZC CAPD YE

4 A B C D

5 A B C D E F G

6 A TATA CCAATB DNAC 5 D 3 E

7 A B C RNAD DNAE DNA I

8 A B C D E

9 A B C D E

10 RNAA B C RNAD RNAE A

11 A B C D E

12 A B C D E

13 A B C D E

14 A B C D E

15 A B C D E

16 DNADNA A B C D E

17 A B C D E

18 A TATA CCAATB DNAC 5 D 3 E

19 A CAPB CAPC CAPD CAPE CAP

20 A B C D E