Regulation and control of gene expression

Chapter 14

Section 1Basic concepts and

principles

一 、一 、 Concepts of gene expressioConcepts of gene expressionn

* The whole set of genetic information or genes of haploid cell virus is known as genome.

The process in which gene is transcribed and translated so to produce protein molecules with special biological function.

* gene expression

gene expression is controlable.

二、二、 Characteristics of gene expressionCharacteristics of gene expression

（一） temporal specificity

According to the requirement of function, the expression a given gene occurs exactly according to the temporal sequence.

Temporal specificity of the expression of gene in multicellular organism is also known as phase specificity.

（二） Spacial specificity

The difference of distribution of gene expression following the temporal sequence is actually determined by the distribution of cells in organs so that the spacial specificity is also known as cellular specificity or tissue specificity.

During the whole process of the growth of individual body, the product of a given gene appears according to the sequence of different tissue space.

三、三、 The manner of gene expressionThe manner of gene expressionAccording to the reactivity to stimulus, gene expression is divided into ：

（一） constitutive expression

No matter high or low level expression, housekeeping genes are seldom influenced by environmental elements. They are expressed continuously in most or all of tissues in every phase of growth. This kind of gene expression is known as constitutive expression.

Some genes are expressed continuously in almost all of cells in a body. They are known as housekeeping genes.

（二） Induction expression and repression expressoin

Under the stimulation of a given environmental signal, the gene is activated, and the product from gene expression is increased. This kind of gene is known as inducible gene.The process of the augment of the expression of the inducible gene in a given environment is known as induction.

If the response of the gene to environmental signal is being repressed. This kind of gene is repressible gene.The process of the decrease of the expressed product of repressible gene is knows as repression.

Under the control of certain mechanism, a group of genes related by function must coordinate and express simultaneously no matter what kind of expression manner they have. This kind of gene expression is namely coordinate expression. This kind of regulation is known as coordinate regulation.

四、四、 Biological significance of the regBiological significance of the regulation of gene expressionulation of gene expression

（一） conform to environment, maintain the growth and proliferation.

（二） maintain the development and differentiation of the individual body.

五、五、 Basic principles of the regBasic principles of the regulation of gene expressionulation of gene expression

（一） multilevel regulation of gene expression

gene activation

initiation of transcription post-transcriptional processingmRNA degradation

translationpost-translational processingprotein degradation

（二） Basic elements for the regulation on

activation of gene transcriptionThe regulation of gene expression is related to the structure and characteristics of gene, the inner and outer environment of organism, and transcription-regulating proteins in cells.1 Special DNA sequence and protein factors

prokaryote

protein factors

------ operon mechanism

special DNA sequece

other regulative sequence

(promoter)

(operator)

coding sequence

TTGACA TATAAT consensus sequence

DNA sequence recognized and bound by RNA polymerase

1) promoter

consensus sequence （ DNA ） determin

es the transcription activity of promoter.

Some special factors （ protein ）

determines the specific recognition a

nd binding ability of RNA polymeras

e to a or a set of promoters.

2operator ——binding site of repressor

The binding of repressor to operator will interrupt the binding of RNA polymerase to promoter, or the movement of RNA polymerase along with DNA so to interrupt transcription.

promoter operatorpol repressor coding sequence

3) other regulating sequence and regulating proteins

For instance ：Activator can bind to the DNA sequence adjacent to promoter so to promote the binding of RNA polymerase to promoter and enhance the activity of RNA polymerase.

RNA polymerase can not bind to the promoter of some genes in the absence of activators.

Eukaryote1) cis-acting element

----DNA sequence which can influence the expression of the gene it belongs.

B A

DNAcoding sequence

transcription initiation site

Cis-acting elements in different eukaryotes contain some consensus sequences such as TATA box and CAAT box which are the binding sites of RNA polymerase or specific transcription factors.

2) Regulation protein of eukaryotic genes

Some protein factors can recognize and bind to the regulative sequence of the gene it belongs so to regulate the expression of the gene. This action is known as cis-action.

They are proteins produced by one gene and can interact with the cis-acting element of another gene so to regulate the expression of the gene.

trans-acting factors

This action is known as trans-action.

The recognizable DNA-binding site is usually symmetric or incompletely symmetric structure.

Before the binding to DNA, most of regulative

proteins need to form dimer or multimer thro

ugh protein-protein interaction.

二、 Interaction of DNA-protein and

protein-protein

三 RNA polymerase1 prokaryotic promoter / eukaryotic promoter

The affinity of RNA polymerase to promoter influences transcription.

2 regulative proteins

Some specific proteins are produced after stimulation of environmental signals, and then, they influence the activity of RNA polymerase through the interaction of DNA-protein and protein-protein.

Regulation of Regulation of prokaryotic genes at prokaryotic genes at transcription leveltranscription level

Section 2Section 2

一、 Characteristics of regulation of transcription of prokaryotic genes

( 一 ) σ factor determines the specificity of the recognition of RNA polymerase

( 二 ) The universality of operon model

( 三 ) The universality repressor and repression mechanism

二、 Regulation mechanism of lactose operon

( 一 ) Structure of lactose operon

regulative region

CAP binding site

promoter

operator

structure genes

Z ： β-galactosidase

Y ： permease

A ： galactoside acetylase

Z Y AOPDNA

CAP: catabolite gene activator protein

in the absence of lactose

( 二 ) negative regulation of repressor

in the presence of lactose

lactose

cAMP is high in the absence of glucose

cAMP is low in the presence of glucose

( 三 ) positive regulation of CAP

( 四 ) coordinate regulation ※ if repressor blocks transcription, CAP will not work.

※ Operon is inactive without CAP, even in the absence of repressor.

if only lactose is present, bacteria use lactose as carbon source.

if both glucose and lactose are present, bacteria use glucose first.

The repression of glucose to lac operon is known as catabolic repression.

low lactose high lactose

glucose low cAMP high

glucose high cAMP low

三 Other regulation mechanism of transcription

( 一 ) attenuation of transcriptionregulation region structure genes

tryptophan operon

1 、 trp high

mechanism of transcription attenuation:

2 、 trp low

( 二 ) gene recombination

H1 flagellum protein

regulation of flagellum protein of salmonnella gene

( 三 ) SOS reaction

SOS genes

UV light

activationRec A

Lex A 阻遏蛋白

enzymes and proteins

related with DNA repair

gene expression

Lex A repressor

operatorDNA

Section 3 Regulation of

eukaryotic genes at transcription level

Section 3 Regulation of eukaryotic genes at transcription level

一 Characteristics of eukaryotic genome

( 一 ) eukaryotic genome is huge

mammalian genome

DNA: about 3 × 109 base pairs

about 30000 structure genes ， 6 % of the total length

rDNA: about 5% ~ 10%

( 二 ) monocistron

mRNA molecule from one coding gene produces one peptide chain after translation.

( 三 ) repetitive sequences

single copy sequence

highly repetitive sequence （ 106 ）

moderately repetitive sequence （ 103~ 104 ）

multicopy sequences

( 四 ) incontinuity of genes

二 characteristics of regulation of eukaryotic gene expression

( 一 ) RNA polymerase

( 二 ) change of structure of chromosome

1 、 sensitive to nuclease

Active gene has supersensitive site which is adjacent to binding site of regulative protein.

2 、 change of topological structure of DNA

native double-stranded DNA are present as negative super-helix.

after activation of gene ，

RNA-pol positive super-helix

negative super-helix

direction of transcription

3 、 change of base modification of DNA

Cytosines of 5% of eukaryotic DNA are methylated.

the extent of methylation is negatively proportional to the extent of gene expression.

CpG sequence

4 、 change of histones

① the level of Lys-rich histones is reduced.

② instability of H2AH2B dimer increases.

③ modification of histones.

④ sulfhydryl group of H3 histone is exposed.

( 三 ) Positive regulation dominates.

( 四 ) transcription and translation are performed seperately

( 五 ) Post-transcriptional modification , processing

三 regulation of transcription activation of eukaryotic genes

( 一 ) cis-acting elements

1 、 promoter Eukaryotic promoter is a group of transcription-controlling elements around the binding site of RNA polymerase, including at least a transcription initiation site and more than one functional element.

TATA box

GC box

CAAT box

2 、 enhancer

DNA sequences which are some distance from transcription initiation site, determine the temporal and spacial specificity, enhance the transcription activity of promoter.

3 、 silencer

negative regulatory elements of some genes. they repress the transcription of gene if they are bound by specific protein factors.

( 二 ) trans-acting factors

1 、 classification according to function

* Basic transcription factors

A group of protein factors which are necessary f

or the binding of RNA polymerase, and determine

the type of one of three kind of RNAs (mRNA, tRN

A and rRNA ).

* specific transcription factors

Factors which are needed by individual gene,

and determine the temporal and spacial specifici

ty of gene expression.

transcription activation factors

transcription repression factors

2 、 Structure of transcription regulatory factors

DNA-binding domain

transcription activation domain

TF

protein-protein binding domain

（ dimerization domain ）

glutamine-rich domain

proline-rich domain

acidic activation domain

DNA-binding domain:

1 、 zinc finger

C —— Cys

H —— His

usually binds to GC box

( 三 ) transcription activation and its regulation of mRNA

Eukaryotic RNA polymerase forms transcripⅡtion initiation complex with the help of transcriptoin factors.

regulation of transcription of eukaryotic genes is complicated and multiplex ：

* The combination of different DNA elements can produce multiple-types of manner of transcription regulation. * many transcription factors can bind to same or different DNA elements.

* The binding of transcription factors to DNA elements produce different effect to the process of transcription activation, either positive regulation or negative regulation.