The Cell - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 18

1.5 Transcriptional Control of Gene Expression
Gene expression is regulated by regulatory factors at various levels so that a differen-
tial synthesis of protein is observed. This is important if proteins are being produced
in anatomically and physiologically different cells or in different development stages
or in response to various external stimuli. The regulation of gene expression in pro-
karyotes is with the basic aim to help the organism meet the challenges of survival
in accordance to the external conditions and to optimize its growth. Gene expression
regulation in eukaryotes has several different objectives to meet. These include dif-
ferentiation during development, immune response development, and so on. In spite
of the difference in purpose of regulation, there are some basic features common to
both the gene regulatory sequences and control elements associated with genes. Gene
regulatory proteins bind to these elements to enhance or suppress gene expression.
Activator proteins promote binding of RNA polymerase to the promoter region,
whereas repressor proteins inhibit this association. These protein binding sites are
often located close to or at distant locations from the site of initiation. There are three
types of RNA polymerases in eukaryotes. RNA polymerase I is involved in the syn-
thesis of pre-rRNA, RNA polymerase II synthesizes mRNA, and RNA polymerase III
synthesizes tRNA and some other small RNA molecules. Promoter regions are impor-
tant in regulating binding of RNA polymerase II to influence the site of initiation and
rate of transcription. Three types of important promoter regions have been identified
in eukaryotes. These include TATA boxes, initiators, and CpG islands. Further, addi-
tional cell-specific elements like enhancers and promoter proximal elements located
upstream or downstream play a role in gene expression regulation. Corresponding
elements called repressors are functionally opposite to activators. Transcription acti-
vators or repressors have a unique single-DNA binding site and one or more activat-
ing or repressing regions in their three-dimensional conformation. There are some
common structural conformations in the DNA-binding domains of transcription fac-
tors like C 2 H 2 zinc finger, homeodomain, basic zipper, and basic loop-helix-loop.
These structures have alpha helices that interact with the major groove in the DNA.
Similarly, activation and repression domains have a diverse three-dimensional con-
formation and bind with coactivators and repressors to eventually modulate the gene
expression. Thus, a very complex process involving several proteins and genetic ele-
ments is important to the regulation of gene expression [52-56] .
1.6 Cell Communication or Biosignaling
For the cell to maintain homeostasis, it must respond to changes in its environment.
This prepares the cell for a defensive, proactive reaction or helps it in acquiring
nutrition and so on. This process requires signal transduction, which is the conver-
sion of signals like pH, osmotic strength, oxygen, light, and so on, into a chemical
change. The basis of cellular communication, or biosignaling, is that a specific signal
is identified by the receptor proteins in the target cell, and in response to the
signal an appropriate response is elicited. Signal transmission may be widespread, as