section 26.4
Mechanisms of Gene Regulation
motif is repeated nine times in TFIIA protein. The 12
amino acids between the cysteine and histidine
residues form a loop that can interact with the major
groove in DNA; this loop is called the “zinc finger.”
Leucine zipper:
The structure of the leucine zipper
(first discovered in C/EBP, CCAAT, and enhancer
binding protein) consists of four leucine residues in
an a-helical segment of the protein. Two polypeptides
join to form a Y-shaped dimer whose arms can interact
with the major groove of DNA. The stem of the
Y-shaped structure is known as the “leucine zipper.”
Helix-turn-helix (HTH):
This structure (first
discovered in the A
. bacteriophage repressors, cl and
cro) consists of two a-helical regions of a protein
joined by an amino acid sequence that allows the
helices to turn. The two a helices form a dyad axis
of symmetry, a structure that binds tightly to the
major groove of DNA.
Helix-loop-helix (HLH):
This structure is similar to
the helix-turn-helix in that it consists of two a-helical
segments joined by a long sequence of amino acids
that can form a loop. This gives the two a-helical
segments more flexibility so that the proteins can fit
into the large groove of DNA at some distance from
one another. This may facilitate looping of the DNA
to make enhancer or promoter sites more accessible.
The serum albumin gene is one example of a gene that
is regulated by several transcription factors. Although this
gene is present in all tissues, it is only expressed in liver and
spleen. The gene is activated by five different transcription
factors that bind DNA in a region located between the
CCAAT and TATA boxes (Figure 26-8). The transcription
factor NF-1
actually binds to the right of the CCAAT box.
Binding sites for transcription factors are determined by
changing bases in the DNA one at a time and observing
changes in the binding of transcription factors.
Steroid Receptors
Steroid hormones perform many functions in cells, one
of which is to activate gene expression by binding to
steroid receptors,
proteins in the cytoplasm that, when
activated, act as factors that initiate transcription. All
steroid hormones are derived from cholesterol and, as
a result, have similar chemical structures. Steroid hor-
mones differ one from another primarily in hydrox-
ylation of particular carbon atoms and by aromatiza-
tion of the steroid A ring of the molecule. Once a
steroid hormone binds to a steroid receptor protein, the
complex undergoes a series of structural changes that
result in the complex binding to DNA at a particu-
lar sequence called a
steroid response element
F I G U R E 2 6 -8
Expression of the human serum albumin gene is regulated by five transcription factors, four of which bind to the
promoter region.
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