第六章 Regulation of transcription
in eukaryotes
一、构成性转录因子 SP1对持家基因的调控作用
1,Housekeeping （ constitutive） genes （持家
基因）, 细胞内的蛋白质编码基因，维持细胞的基
本过程。
2,SP1结合于保守性序列 GGGCGG的 GC丰富
序列，该序列位于许多持家基因的启动子中。
3,SP1含有, 3 zinc finger motifs which bind to
GC-rich sequance,2个 glutamine-rich domains
interact with TAFII110 of TFII D
GC
SP1 TBPSP1
110
TBP
The specific transcription factor SP1binds to
GC rich sequence in TATA less promoter
glutamine-rich
domains
zinc finger motifs
二,Hormone regulation,
Hormones are molecules
which are secreted by one
specific cell type and transmit a
signal to a target cell type.
（ 1）,Steroid hormone and their
receptors
1,Steroid hormones,lipid soluble and can
diffuse through cell membranes to interact with
transcription factor,steroid hormone receptors.
2,Steroid hormones：
glucocorticoid 糖皮质激素
estrogen 雌激素 retinoic acid 视黄酸
thyroid 甲状腺素
3,General steroid model of gene transcription
activation
Glucocorticoid
GRE
receptor
inhibitor
Nuclear
translocation
（ 2）,Regulation by phosphorylation
Interferon-?
cell-surface receptor
signal transduction process
Janus activated kinase 两面神蛋白激酶
STAT? signal transduction and
transcription factor
Phosphorylation at tyrosine residue
homodimer 同源二聚体
p p
P p
Interferon
Interferon
receptor
JAK Kinase
Unphosphrylation
STAT? monomers +2ATP +2ADP
Phosphorylated
STAT? dimer
Response element
nuclear
三,Activation of transcription elongation
by HIV Tat protein
1,Tat encoded by HIV is required for productive
HIV gene expression;
2,Tat binds to an RNA stem-loop structure called
TAR,located at the 5’-untranslated region of all
HIV RNAs;
3,The protein-RNA complex may loop
backwoards and interact with the new initiation
complex,resulting activation of the kinase activity
of TFIIH
TatCellularfactor
RNA Polymerase
H CTD p
The mechanism of HIV Tat-TAR complex
Tat-Tar cellular factor
complex activates TFIIH
Activated TFIIH phosphorylates
CTD of RNA pol II
四,Gene for cell determination,myoD
Somites 体节 fibroblasts
（ Mesodermal embryonic cell
中胚层细胞 ） overexpression
of myoD
myotomes 生肌节 muscle-like cells.
（ skeletal muscle cell）
myoblasts (成肌细胞, muscle cell)
成纤维细胞
myoD
expression
myoD p21/waf/cip1
activates
MyoD p21/waf/cip1 CDKs cell cycle
activates ( cyclin dependent kinase)
muscle specific arrest
gene expression at the G1-phase.
Cell differentiation
1,MyoD activates muscle-specific gene expression
*
There have now been shown to be four genes,
myoD,myogenin,myf5 and mrf4,the expression of
each of which has ability to convert fibroblasts into
muscle,
The encoded proteins are all members of of the
HLH TF family.
The HLH group of proteins produce a diverse
range of hetro- and homodimeric TFs that each
have different activities and roles.
HLH结构特征
2,Inhibitor:Id
These proteins are regulated by an inhibitor called
Id that lacks a DNA binding domain,but contains
the HLH dimerization domain.
Therefore,Id protein can bind to MyoD and
related protein,but the resulting heterodimers
cannot regulate transcription.
五,Embryonic development:
homeodomain proteins
The homeobox is a conserved DNA sequence which
encodes the HTH DNA binding protein structure
called the homeodomain,containing a 60 amino
acid domain,This structure was first discovered in
Drosophila,
Homeotic genes are responsible for correct
specification of body parts,For example,mutation
of one of these genes,Antennapedia (触角足 ),cause
the fly to form a leg where the antenna should be.
The homeobox genes are arranged in gene
clusters in which homologous genes are in
the same order both in Drosophila and
mammals.
The gene homologs are also expressed in a
similar order in embryo on the anterior
(前端 ) to posterior（后端） axis.
in eukaryotes
一、构成性转录因子 SP1对持家基因的调控作用
1,Housekeeping （ constitutive） genes （持家
基因）, 细胞内的蛋白质编码基因，维持细胞的基
本过程。
2,SP1结合于保守性序列 GGGCGG的 GC丰富
序列，该序列位于许多持家基因的启动子中。
3,SP1含有, 3 zinc finger motifs which bind to
GC-rich sequance,2个 glutamine-rich domains
interact with TAFII110 of TFII D
GC
SP1 TBPSP1
110
TBP
The specific transcription factor SP1binds to
GC rich sequence in TATA less promoter
glutamine-rich
domains
zinc finger motifs
二,Hormone regulation,
Hormones are molecules
which are secreted by one
specific cell type and transmit a
signal to a target cell type.
（ 1）,Steroid hormone and their
receptors
1,Steroid hormones,lipid soluble and can
diffuse through cell membranes to interact with
transcription factor,steroid hormone receptors.
2,Steroid hormones：
glucocorticoid 糖皮质激素
estrogen 雌激素 retinoic acid 视黄酸
thyroid 甲状腺素
3,General steroid model of gene transcription
activation
Glucocorticoid
GRE
receptor
inhibitor
Nuclear
translocation
（ 2）,Regulation by phosphorylation
Interferon-?
cell-surface receptor
signal transduction process
Janus activated kinase 两面神蛋白激酶
STAT? signal transduction and
transcription factor
Phosphorylation at tyrosine residue
homodimer 同源二聚体
p p
P p
Interferon
Interferon
receptor
JAK Kinase
Unphosphrylation
STAT? monomers +2ATP +2ADP
Phosphorylated
STAT? dimer
Response element
nuclear
三,Activation of transcription elongation
by HIV Tat protein
1,Tat encoded by HIV is required for productive
HIV gene expression;
2,Tat binds to an RNA stem-loop structure called
TAR,located at the 5’-untranslated region of all
HIV RNAs;
3,The protein-RNA complex may loop
backwoards and interact with the new initiation
complex,resulting activation of the kinase activity
of TFIIH
TatCellularfactor
RNA Polymerase
H CTD p
The mechanism of HIV Tat-TAR complex
Tat-Tar cellular factor
complex activates TFIIH
Activated TFIIH phosphorylates
CTD of RNA pol II
四,Gene for cell determination,myoD
Somites 体节 fibroblasts
（ Mesodermal embryonic cell
中胚层细胞 ） overexpression
of myoD
myotomes 生肌节 muscle-like cells.
（ skeletal muscle cell）
myoblasts (成肌细胞, muscle cell)
成纤维细胞
myoD
expression
myoD p21/waf/cip1
activates
MyoD p21/waf/cip1 CDKs cell cycle
activates ( cyclin dependent kinase)
muscle specific arrest
gene expression at the G1-phase.
Cell differentiation
1,MyoD activates muscle-specific gene expression
*
There have now been shown to be four genes,
myoD,myogenin,myf5 and mrf4,the expression of
each of which has ability to convert fibroblasts into
muscle,
The encoded proteins are all members of of the
HLH TF family.
The HLH group of proteins produce a diverse
range of hetro- and homodimeric TFs that each
have different activities and roles.
HLH结构特征
2,Inhibitor:Id
These proteins are regulated by an inhibitor called
Id that lacks a DNA binding domain,but contains
the HLH dimerization domain.
Therefore,Id protein can bind to MyoD and
related protein,but the resulting heterodimers
cannot regulate transcription.
五,Embryonic development:
homeodomain proteins
The homeobox is a conserved DNA sequence which
encodes the HTH DNA binding protein structure
called the homeodomain,containing a 60 amino
acid domain,This structure was first discovered in
Drosophila,
Homeotic genes are responsible for correct
specification of body parts,For example,mutation
of one of these genes,Antennapedia (触角足 ),cause
the fly to form a leg where the antenna should be.
The homeobox genes are arranged in gene
clusters in which homologous genes are in
the same order both in Drosophila and
mammals.
The gene homologs are also expressed in a
similar order in embryo on the anterior
(前端 ) to posterior（后端） axis.
