Biology Reference
In-Depth Information
Regulation of transcription is the most common method of gene regulation in
eukaryotes. mRNA molecules generally are short-lived, probably persisting a few
minutes or hours. Rapid turnover means that by adjusting the rate of transcrip-
tion the amount of a particular mRNA in the cell can be controlled. Both nega-
tive and positive transcriptional regulation can occur.
Transcriptional regulation involves
transcriptional activator proteins
that bind
with an upstream DNA sequence to prepare a gene for transcription. They may
help assemble a transcriptional complex, or they may initiate transcription by an
already-assembled transcriptional complex. Some transcriptional activator pro-
teins have a helix-turn-helix structure, i.e., a sequence of amino acids that form
a pair of
α
-helices separated by a bend. These helices fit into the grooves of a ds
DNA molecule and allow the proteins to bind to the DNA, although the specific-
ity of the binding is determined by other parts of the protein (
Harrison 1991
).
Examples of helix-turn-helix DNA-binding proteins in insects include the
homeo
domain
, a domain found in genes such as
engrailed
+
and
Antennapedia
+
that
are important in regulating development of
D. melanogaster
(described in more
detail in Chapter 4).
Zinc-finger proteins
are a second type of transcriptional activator protein.
They are characterized by loops (fingers) of repeating amino-acid sequences
each associated with a zinc atom. Zinc-finger proteins bind in the major groove
of the DNA helix (
Figure 2.9)
of an upstream DNA sequence to prepare a gene
for transcription.
Leucine zippers
are a third type of DNA-binding protein. Leucine zippers are
DNA-binding proteins that contain four to five leucine residues separated from
each other by six amino acids. The leucines on two protein molecules can inter-
digitate and dimerize in a specific interaction with a DNA recognition sequence
(
Abel and Maniatis 1989
).
Hormones may turn on the transcription of specific sets of genes. For exam-
ple, steroid hormones penetrate a target cell through diffusion because ste-
roids pass freely through the cell and nuclear membranes. The nuclei of target
cells contain specific receptor proteins that form complexes with the hormone;
these complexes then undergo modification in their three-dimensional forms,
enabling the receptor-hormone complexes to bind with particular sequences
in the DNA and stimulate or repress transcription. In the lepidopteran
Manduca sexta
,
ecdysone
, a steroid, acts directly on the genome both to
activate and repress genes. Ecdysone initiates and coordinates the molting
process and thus the sequential expression of stage-specific genes (
Riddiford
et al. 1990
).
