N1 Eukaryotic transcription factorsN1 Eukaryotic transcription factors
Transcription factor domain structure, DNA- binding
domains, Dimerization domains,Transcription
activation domains, Repressor domains,Targets for
N2 Eukaryotic of transcriptionalN2 Eukaryotic of transcriptional
Constitutive transcription factors:SP1, Hormonal
regulation: steroid hormone receptors, Regulation by
phosphorylation: STAR proteins,Transcription
elongation: HIV Tat, Cell determination: myoD,
Embrynic development: homeodomain proteins
Transcription of a single gene may be regulated by
many different factors interacting with regulatory
elements upstream or downstream of the
to bind transcription factors
1.1. The helix-turn-helix domainThe helix-turn-helix domain
2.2. The zinc finger domainThe zinc finger domain
3.3. The basic domainThe basic domain
1). Homeodomain: encoded by a sequence
called the homeobox, containing a 60-
amino-acid. In the Antennapedia
transcription factor of Drosophila, this
domain consists of four α-helices in
which helices and are at right anglesⅡ Ⅲ
to each other and are separated by a
Examples of Helix-turn-helix
2). Bacteriophage DNA-binding proteins
such as the phage cro repressor, lacλ
and trp repressors, and cAMP receptor
The recognition helix of the domain
structure lies partly in the major groove
and interacts with the DNA.
The recognition helices of two
homeodomain factors Bicoid and
Antennapedia can be exchanged, and this
swaps their DNA-binding specificities.
Zinc finger domain exists in
a. C2H2 zinc finger: a loop of 12 amino
acids anchored by two cysteine and
two histidine residues that
tetrahedrally co-ordinate a zinc ion.
This motif folds into a compact
structure comprising two β-strands
and one α-helix. The α-helix
containing conserved basic amino
acids binds in the major groove of
(1) TFIIIA, the RNA Pol III
transcription factor, with C2H2zinc
finger repeated 9 times.
(2) SP1, with 3 copies of C2H2zinc
Usually, three or more C2H2zinc
fingers are required for DNA
b. C4 zinc finger: zinc ion is
coordinated by 4 cysteine
Example: steriod hormone receptor
transcription factors (N2) consisting of
homo- or hetero-dimers, in which each
monomer contains two C4 zinc finger.
The helix-loop-helix domain
Leucine zipper proteins contain a
hydrophobic leucine residue at every
seventh position in a region that is
often at the C-terminal part of the
DNA-binding domain .
These leucines are responsible for
dimerization through interaction
between the hydrophobic faces of the
-helices.This interaction forms aα
bZIP (basic leucine zipper) transcription
factors: contain a basic DNA-binding domain
N-terminal to the leucine zipper.The N-
terminal basic domains of each helix form a
symmetrical structure in which each basic
domains lies along the DNA in opposite
direction, interacting with a symmetrical DNA
recognition site with the zippered protein
The leucine zipper is also used as a
dimerization domain in proteins containing
DNA-binding domains other than the basic
domain, including some homeodomain
The helix-loop-helix domain
The overall structure is similar to
the leucine zipper, except that a
nonhelical loop of polypeptide chain
separates two -helices in eachα
Hydrophobic residues on one side of
the C-terminal -helix allowα
Example: MyoD family of proteins.
Similar to leucine zipper, the HLH
motif is often found adjacent to a
basic domain that requires
dimerization for DNA binding.
Basic HLH proteins and bZIP
proteins can form heterodimers
allowing much greater diversity and
complexity in the transcription factor
Also called “acid blobs” or
Rich in acidic amino acids
Exists in many transciption
1. yeast Gcn4 and Gal4,
2. mammalian glucocorticoid
3. herpes virus activatorVP16
Acidic activation domains
Rich in glutamine
the proportion of glutamine
residued seems to be more
important than overall structure.
Exists in the general
transcription factor SP1.
continuous run of proline
residues can activate
Exists in transcription factors c-
jun, AP2 and Oct-2.
Repression of transcription may occur by
indirect interference with the function of
an activator.This may occur by:
Blocking the activator DNA-binding site
(as with prokaryotic repressors, wrong)
Formation of a non-DNA-binding
complex (e.g. the Id protein which blocks
HLH protein-DNA interactions, since it
lacks a DNA-binding domain, N2).
3. Masking of the activation domain without
preventing DNA binding (e.g. Gal80 masks the
activation domain of the yeast transcription
A specific domain of the repressor is directly
responsible for inhibition of transcription. (e.g.
e.g. A domain of the mammalian thyroid
hormone receptor can repress transcription
interaction with TFIID through specific
interaction with TFIIB;
interaction or modulation of the TFIIH
complex activity leading to differential
posphorylation of the CTD of RNA Pol II.
It seems likely that different
activation domains may have
different targets, and almost any
component or stage in initiation
and transcription elongation
could be a target for regulation
resulting in multistage
regulation of transcription.
binds to a GC-rich sequence with the
consensus sequence GGGCGG.
binding site is in the promoter of many
It is a constitutive transcription factor present in
all cell types.
contains three zinc finger motifs and two
glutamine-rich activation domains interacting
with TAFII110, thus regulating the basal
Many transcription factors are activated
by hormones which are secreted by one
cell type and transmit a signal to a
different cell type.
steroid hormones: lipid soluble and can
diffuse through cell membranes to
interact with transcription factors called
steroid hormone receptors.
In the absence of steroid hormone,
the receptor is bound to an inhibitor,
and located in the cytoplasm.
In the presence of steroid hormone,
1. the hormone binds to the receptor
and releases the receptor from the
2. receptor dimerization and
translocation to the nucleus.
3. receptor interaction its specific DNA-
binding sequence (response element)
via its DNA-binding domain,
activating the target gene.
Steroid hormones involving
important hormone receptors:
glucocorticoid ( 糖皮质激素） ,
estrogen ( 雌激素 ), retinoic acid
（视黄酸） and thyroid hormone
Please noted that the above model is
not true for all these hormone receptors
Thyroid hormone receptor is a DNA-
bound repressor in the absence of
hormone, which converted to a
For hormones that do not diffuse into the
The hormones binds to cell-surface
receptors and pass a signal to proteins
within the cell through signal transduction.
Signal transduction often involves protein
Example: Interferon- inducesγ
phosphorylation of a transcription factor
called STAT1 through activation of theα
intracellular kinase called Janus activated
1. Unphosphorylated STAT1 protein:α
exists as a monomer in the cell
cytoplasm and has no
2. Phosphorylated STAT1 at aα
specific tyrosine residue forms a
homodimer which moves into the
nucleus to activate the expression
of target genes whose promoter
regions contain a consensus DNA-
Human immunodeficiency virus (HIV)
(pic…) encodes an activator protein
called Tat, which is required for
productive HIV gene expression(pic..).
Tat binds to an RNA stem-loop structure
called TAR, which is present in the 5’-UTR
of all HIV RNAs just after the HIV
transcription start site, to regulate the
level of transcription elongation.
In the absence of Tat, the HIV
transcripts terminate prematurely due
to poor processivity of the RNA Pol Ⅱ
Tat binds to TAR on one transcript in a
complex together with cellular RNA-
binding factors.This protein-RNA
complex may loop backwards and
interact with the new transcription
initiation complex which is assembled
at the promoter.
This interaction may result in the
activation of the kinase activity of
TFIIH, leading to phosphorylation of
the carboxyl-terminal domain (CTD) of
RNA Pol , making the polymerase aⅡ
processive enzyme to read through the
HIV transcription unit, leading to the
productive synthesis of HIV proteins
myoD was identified as a gene to regulate gene
expression in cell determination, commanding cells to
MyoD protein has been shown to activate muscle-
specific gene expression directly. Overexpression of
myoD can turn fibroblasts into muscle-like cells which
express muscle-specific genes and resemble
myoD also activates expression of p21waf1/cip1
expression, a small molecule inhibitor of CDKs, causing
cells arrested at the G1-phase of the cell cycle which is
characteristic of differentiated cells. .
Four genes,myoD,myogenin, myf5 and
mrf4 have been shown to have the ability
to convert fibroblasts into muscle.The
encoded proteins are all members of the
helix-loop-helix (HLH for dimerization)
transcription factor family.
These proteins are regulated by an
inhibitor called Id that lacks a DNA-
binding domain, but contains the HLH
dimerization domain. Id protein can bind
to MyoD and related proteins, but the
resulting heterodimers cannot bind DNA,
and hence cannot regulate transcription
The homeobox is a conserved DNA sequence
which encodes the helix-turn-helix DNA
binding protein structure called the
Homeotic genes of Drosophila are responsible
for the correct specification of body parts. For
example, mutation of one of these genes,
Antennapedia, causes the fly to form a leg
where the antenna should be.
conserved between a wide range of
important in mammalian development.
1. Which two of the following statements about transcription factors are true?
A the helix-turn-helix domain is a transcriptional activation domain.
B dimerization of transcription factors occurs through the basic domain.
C leucine zippers bind to DNA.
D it is often possible to get functional transcription factors when DNA binding
domains and acti-vation domains from separate transcription factors are fused
E the same domain of a transcription factor can act both as a repressor and as an
2 ． Which two of the following statements about transcriptional regulation are
A SP1 contains two adivation domains.
B steroid hormones regulate transcription through binding to cell surface receptors.
C phosphorylation of Stat1 leads to its migration from the cytoplasm to the nucleus.α
D HIV Tat regulates RNA Pol II phosphorylation and processivity.
E the MyoD protein can form heterodimers with a set of other HLH transcription
F the homeobox is a conserved DNA binding domain.