16 Control of Gene Expression

1) Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product.

The process of gene expression is used by all known life - eukaryotes, prokaryotes and viruses - to generate the macromolecular machinery for life

Regulation of gene expression refers to the control of the amount and timing of appearance of the functional product of a gene. Control of expression is vital to allow a cell to produce the gene products it needs when it needs them; in turn this gives cells the flexibility to adapt to a variable environment, external signals, damage to the cell, etc. Some simple examples of where gene expression is important are:

• Control of Insulin expression so it gives a signal for blood glucose regulation

• X chromosome inactivation in female mammals to prevent an "overdose" of the genes it contains.

Generally gene regulation gives the cell control over all structure and function, and is the basis for cellular differentiation, morphogenesis and the versatility and adaptability of any organism.

2) Transcriptional regulation

Regulation of transcription can be broken down into three main routes of influence; genetic (direct interaction of a control factor with the gene), modulation (interaction of a control factor with the transcription machinery) and epigenetic (non-sequence changes in DNA structure which influence transcription).

• Direct interaction with DNA is the simplest and the most direct method by which a protein can change transcription levels. Genes often have several protein binding sites around the coding region with the specific function of regulating transcription. There are many classes of regulatory DNA binding sites known as enhancers, insulators, repressors and silencers. The mechanisms for regulating transcription are very varied, from blocking key binding sites on the DNA for RNA polymerase to acting as an activator and promoting transcription by assisting RNA polymerase binding.

• The activity of transcription factors is further modulated by intracellular signals causing protein post-translational modification including phosphorylated, acetylated, or glycosylated. These changes influence a transcription factor's ability to bind, directly or indirectly, to promoter DNA, to recruit RNA polymerase, or to favor elongation of a newly synthetized RNA molecule.

• The nuclear membrane in eukaryotes allows further regulation of transcription factors by the duration of their presence in the nucleus which is regulated changes in their structure and by binding of other proteins. Environmental stimuli or endocrine signals may cause modification of regulatory proteins, which result in regulation of gene expression.

• In eukaryotes, DNA is organized in form of nucleosomes. DNA is tightly wrapped around the protein core made of histone octamer, restricting access to the DNA. Eukariotic cells can regulate transcription through modulation of nucleosome structure or modification of histone terminal chains, which are unbinded to dna.

• DNA methylation is a widespread mechanism for epigenetic influence on gene expression and is seen in bacteria and eukaryotes. In eukaryotes the structure of chromatin, controlled by the histone code, regulates access to DNA with significant impacts on the expression of genes in euchromatin and heterochromatin areas.