Topic 5: Regulation of Gene Development and Expression

A segment of the DNA that codes for a specific polypeptide is known as a structural gene. These often occur together on a bacterial chromosome. The location of the polypeptides, which may be enzymes involved in a biochemical pathway, for example, allows for quick, efficient transcription of the mRNAs. Often leader and trailer sequences, which are not translated, occur at the beginning and end of the region. E.coli can synthesize 1700 enzymes. Therefore, this small bacterium has the genes for 1700 different mRNAs. So, gene regulation is necessary to control the outburst of bacteria. There are several methods to control gene expression.

One of these methods of gene regulation is the operon model. The operon model of prokaryotic gene regulation was proposed by Fancois Jacob and Jacques Monod. Groups of genes coding for related proteins are arranged in units known as operons. An operon consists of an operator, promoter, regulator, and structural genes. The regulator gene codes for a repressor protein that binds to the operator, obstructing the promoter (thus, transcription) of the structural genes. The regulator does not have to be adjacent to other genes in the operon. If the repressor protein is removed, transcription may occur. Operons are either inducible or repressible according to the control mechanism. Seventy-five different operons controlling 250 structural genes have been identified for E. coli. Both repression and induction are examples of negative control since the repressor proteins turn off transcription.

The eukaryotic chromosome consists of DNA and proteins that appear to play a major role in regulation of eukaryote genes. The DNA of each chromosome is a long single molecule of double stranded DNA. Eukaryotic DNA comes in two forms. Chromatin is the uncoiled form of DNA and is over 50% protein. Chromosomes are coiled DNA/protein that form during the early stages of cell division. The proteins associated with DNA are collectively known as histones. They are relatively short polypeptides which are positively charged (basic) and thus are attracted to the negatively charged (acidic) DNA. Histones are synthesized in quantity during the S-phase of the cell cycle. One function of theses proteins seems to be the folding and packaging of DNA into chromosome form: the 2 m of DNA in a human cell are packaged into 46 chromosomes with a combined length of 200nm (a nm remember is 10-6m). Some 90 million molecules of histones occur in a single cell, with the majority (30 million) being H1 histones. Five types of histone are known (H1, H2A, H2B, H3, and H4); with the exception of H1, most eukaryote histones are very similar. A nucleosome is the fundamental packing unit of eukaryotic DNA. The core consists of two molecules each of H2A, H2B, H3, and H4; around which the DNA is wound twice. The H1 histone is outside the core. Between 150-200 nucleotide pairs are associated with the core and linker DNA. This level of packing is known as "beads on a string".

As for the replication of the eukaryotic chromosome, nucleotide triphosphates (in the forms ATP, GTP, CTP and TTP) are assembled according to the semi-conservative model. Other details of DNA replication are consistent with what we know for prokaryotes. Eukaryotic DNA has many replication forks and also bidirectional synthesis, contrasting to the unidirectional rolling theta prokaryotic method. Eukaryotic DNA is synthesized much slower than prokaryotic DNA, in humans 50 nucleotides per second per replication fork. After replication the new DNA is immediately associated with histones. Because of multicellularity, the regulation of eukaryotic gene expression can get complex. Each multicellular organism begins as a single-celled zygote which divides by mitosis. Cells differentiate into functional types by using some genes but ignoring others. Homebox genes establish the body plan and position of organs in response to gradients of regulatory molecules. The timing of certain gene expressions seems to follow a sequence, such as the production of different types of fetal hemoglobins by mammalian red blood cells, which switch to adult hemoglobin sometime after birth. Clearly the inactivation of certain genes occurs in every adult cell; therein lies the cure for cancer, old age, etc.