section 26.4

Mechanisms of Gene Regulation

in

Eukaryotes

603

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.”

2.

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.”

3.

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

a

helices to turn. The two a helices form a dyad axis

of symmetry, a structure that binds tightly to the

major groove of DNA.

4.

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

(SRE)

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.