Transcript protein

Chapter 14
Regulation and control
of gene expression
Section 1
Basic concepts and
principles
一 、Concepts of gene expression
* The whole set of genetic information or genes of
haploid cell virus is known as genome.
*
gene expression
The process in which gene is transcribed
and translated so to produce protein
molecules with special biological function.
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
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.
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.
三、The manner of gene expression
According to the reactivity to stimulus, gene
expression is divided into ：
（一） constitutive expression
Some genes are expressed continuously in
almost all of cells in a body. They are
known as housekeeping genes.
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.
（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
The
processgene.
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
The regulation of gene expression
transcription
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
------ operon mechanism
(promoter)
other regulative
sequence
protein
factors
coding sequence
(operator)
special DNA
sequece
1) promoter
TTGACA
DNA sequence recognized and
bound by RNA polymerase
TATAAT
consensus
sequence
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
pol
repressor coding sequence
operator
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.
transcription initiation
DNA
site
B
A
coding sequence
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
trans-acting factors
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.
This action is known as trans-action.
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.
二、Interaction of DNA-protein and
protein-protein
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.
三
1
RNA polymerase
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.
Section
2
Regulation of prokaryotic
genes at transcription level
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
DNA
P
O
operator
promoter
CAP binding
site
structure genes
Z
Y
A
Z： β-galactosidase
Y： permease
A： galactoside acetylase
CAP: catabolite gene activator protein
(二 )
negative regulation of repressor
in the absence of lactose
lactose
in the presence of lactose
(三 )
positive regulation of CAP
cAMP is high in the
absence of glucose
cAMP is low in the
presence of glucose
(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
glucose low
cAMP high
glucose high
cAMP low
high lactose
三 Other regulation mechanism of
transcription
(一) attenuation of transcription
regulation region
structure genes
tryptophan operon
mechanism of transcription attenuation:
1、trp high
2、trp low
(二 )
gene recombination
H1 flagellum
protein
regulation of flagellum protein of salmonnella gene
(三 )
SOS reaction
Lex
repressor
LexA
A阻遏蛋白
DNA
SOS genes
operator
gene
expression
Rec A
activation
UV light
enzymes and proteins
related with DNA repair
Section 3
Regulation of eukaryotic
genes at transcription
level
Section 3
Regulation
of eukaryotic genes at
level
一transcription
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
highly repetitive sequence（ 106）
multicopy sequences
moderately repetitive sequence（ 103~ 104）
single copy sequence
(四 )
incontinuity of genes
二
(一 )
characteristics of
regulation of eukaryotic gene
expression
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，
negative superhelix
RNA-pol
direction of transcription
positive superhelix
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
(一genes
) cis-acting elements
1、promoter
Eukaryotic promoter is a group of transcriptioncontrolling 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
TF
DNA-binding domain
acidic activation domain
transcription
activation
domain
glutamine-rich domain
proline-rich domain
protein-protein binding domain
（dimerization domain）
DNA-binding domain:
1、zinc finger
usually binds to GC
box
C —— Cys
H —— His
(三 )
transcription activation
and its regulation of mRNA
Eukaryotic RNA polymeraseⅡ 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.