Page 395 - Carrahers_Polymer_Chemistry,_Eighth_Edition

358 Carraher’s Polymer Chemistry

activity of the gene.) These so-called active regions are not evenly distributed across the cell’s 23
pairs of chromosomes but are arranged in patches or regions, some being gene-rich and others gene-
poor or deprived. They appear to be sticky, liking to associate with one another. It is similar to the
United States where most of the people occupy a small fraction of the land area with large areas
having only a low population. There are even preferred base sequences for these different regions.
The populated regions tend to be high in C and G sequences whereas nonpopulated areas, regions
were there are few active areas, have higher amounts of A and T sequences. These differences in
preferential sequencing actually help account for the banding found in chromosome patterns. The
light bands are rich in C and G and the dark ones in A and T.
Gene expression simply refers to its transcription resulting subsequently, in most cases, the syn-
thesis of a protein or protein part. The flow of information typically is DNA → RNA → protein →

cell structure and function. Transcription is the term used to describe the transfer of information
from the DNA to RNA; the fl ow of information from the RNA to the protein is called translation.
Genes whose product is needed essentially all the time are present at a constant amount in virtually
every cell. Genes for enzymes of the central metabolic pathways are of this type and are often called
housekeeping genes. Unvarying expression of a gene is called constitutive gene expression.
The cellular levels of some gene products vary with time in response to molecular signals. This
is called regulated gene expression. Gene products that increase in concentration are called induc-
ible and the process of increasing their expression is called induction. Conversely, gene products
that decrease in concentration in response to a molecular signal are said to be repressible and the
process called repression. Transcription is mediated and regulated by protein–DNA interactions.
Thus, while we will focus on the DNA, protein interactions are critical to the operation, expression
of genes.
We are beginning to understand some of the language of the genes. We are already aware of the
sequences that code for particular amino acids. We are also becoming more aware of the meaning of
other sequences. Many of these sequences are involved with transcription regulation. Promoters are
DNA sites where the RNA polymerase can bind leading to initiation of transcription. They are gen-
erally located nearby the gene. There are a number of these sequences. The CAAT box has a con-
sensus sequence of GGCCAATCT and its presence indicates a strong promoter site. One or more
copies of the sequence GGGCGG, called the GC box, are often found upstream from transcription
start sites of housekeeping genes. The TATA box has a sequence of TATAAAA.
Enhancers are DNA sequences that assist the expression of a given gene and may be located
several hundred or thousand base pairs from the gene. They are also called upstream activation
sequences because they exist somewhat removed from transcription start site. Their location varies
between genes. Such sequences are bidirectional occurring the same in both directions.
Response elements are promoter modules in genes responsive to common regulation. Examples
include the heat shock element (HSE) with a sequence CNNGAANNTCCNNG (where “N” is unspec-

ified); the glucocorticoid response element (GRE) with a sequence of TGGTACAAATGTTCT, and
the metal response element (MRE) with a sequence of CGNCCCGGNCNC. HSEs are located about
15 base pairs upstream from a transcription start site of a variety of genes whose expression dra-
matically changes in response to elevated temperatures. The response to steroid hormones depends
on the presence in certain genes of a GRE positioned about 250 base pairs upstream from the tran-
scription start point.
The complexity of these response elements can be seen in considering the metallothionein
gene. Metallothionein is a metal binding protein produced by the metallothionein gene. It protects
against heavy metal toxicity by removing excess amounts from the cell. Its concentration increases
in response to the presence of heavy metals such as cadmium or in response to glucocorticoid hor-
mones. The metallothionein gene promotion package consists of two general promoter elements,
namely a TATA box and GC box; two basal level enhancers; four MREs; and one GRE. These ele-
ments function independently of one another with any one able to activate transcription of the gene
to produce an increase in the metallothionein protein.

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