Regulation and control of gene expression Chapter 14

Section 1 Basic concepts and principles

一 、 Concepts of gene expression * T he 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、 Characteristics 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、 The manner of gene expression According 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、 Biological significance of the regulation of gene expression （一） conform to environment, maintain the growth and proliferation. （二） maintain the development and differentiation of the individual body.

五、 Basic principles of the regulation of gene expression （一） multilevel regulation of gene expression gene activation initiation of transcription post-transcriptional processing mRNA degradation translation post-translational processing protein degradation

（二） Basic elements for the regulation on activation of gene transcription The 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 ） determines the transcription activity of promoter. Some special factors （ protein ） determines the specific recognition and binding ability of RNA polymerase to a or a set of promoters.

2  operator —— 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 operator pol 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.

Eukaryote 1 ) cis-acting element ----DNA sequence which can influence the expression of the gene it belongs. BA DNA coding 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 through protein-protein interaction. 二、 Interaction of DNA-protein and protein-protein

三 RNA polymerase 1 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 prokaryotic genes at transcription level Section 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 ZYAOP DNA 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 lactosehigh lactose glucose low cAMP high glucose high cAMP low

三 Other regulation mechanism of transcription ( 一 ) attenuation of transcription regulation regionstructure 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 activation Rec 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

一 Characteristics of eukaryotic genome ( 一 ) eukaryotic genome is huge mammalian genome DNA: about 3 × 10 9 base pairs about 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 （ 10 6 ） moderately repetitive sequence （ 10 3 ~ 10 4 ） 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 for the binding of RNA polymerase, and determine the type of one of three kind of RNAs (mRNA, tRNA and rRNA ).

* specific transcription factors Factors which are needed by individual gene, and determine the temporal and spacial specificity 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 Ⅱ forms transcription 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.