Biomedical Engineering Reference
In-Depth Information
Polymerase
P1 repressor
P2
G2 Promoter
G2
DNA
Fig. 1.4 Gene expression repression example
can regulate its genes and use its genes selectively, switching genes ON and OFF to
produce different proteins depending on the situation. Or in the case of multicellular
organism, all cells have the same genome and different genes can be expressed to
create large variety of cell types (i.e. skin cells, muscle cells, colon cells, etc.). One
example to demonstrate that the alteration of expression of single gene can trigger
development of a different cell is the study involving fruit flies and gene Ey [ 4 ], which
is crucial for eye development. In this study, Ey is expressed early in development
(using artificial means) in cells that normally go on to form legs. As a result, in these
flies eyes developed in the middle of legs. Another example of single gene expression
affecting cell function is the β -globin gene, which produces one of the hemo protein.
Mutations in the β -globin gene [ 5 ] cause the protein to have the wrong amino acid
sequence and hence, different physical dimension. When this protein binds with the
other hemo protein groups, the resulting hemoglobin does not have the correct shape
to transport oxygen, leading to the disease sickle cell anemia. Both these examples
show how erroneous gene expression can affect normal cell operation and disease.
Protein production can be controlled at different points throughout the transcrip-
tion, translation, and protein binding processes. Of interest to gene regulation and
genomics is the first type, transcription control. Each gene has a start site that in-
dicates where transcription will start. Upstream of the start site on the DNA is the
promoter region (regulatory DNA sequences as shown on Fig. 1.3 ) which are needed
by the cell to switch the gene ON or OFF [ 6 ]. These regulatory DNA sequences must
be bound by gene regulatory proteins which uniquely recognize these sequences.
The gene regulatory proteins, when bounded, can either suppress or enhance tran-
scription. Those proteins which turn OFF genes are called repressors , which proteins
that turn ON genes are activators . For example, when the a repressor binds to the
gene regulatory sequence, the polymerase molecule cannot attach to the starting site,
thus transcription cannot begin and the gene expression is turned off. As shown in
Fig. 1.4 , gene G 1 produces protein P 1, which is a repressor for gene G 2. So if G 1
is expressed ( P 1 is present), then gene G 2 cannot produce protein P 2. Otherwise,
if gene G 1 is not expressed, then gene G 2 can produce protein P 2. In this manner,
a complex gene expression network can be formed.
 
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