Eukaryotic gene controls

All steps—from changes in DNA template, sequence, and accessibility in chromatin to RNA stability—are subject to modulation and hence are potential control sites for eukaryotic gene regulation. 

Owen-Hughes T, Workman JL (1994) Experimental analysis of chromatin function in transcription control. Crit Rev Eukaryot Gene Expr 4 403 41... 

Other mechanisms are important, and, especially in eukaryotes, gene expression is controlled at multiple levels. 

Davie, J.R. and Moniwa, M. (2000) Control of chromatin remodeling. Crit. Rev. Eukaryot. Gene Expr. 10, 303-325. 

Enhancers. Complex DNA sequences called enhancers help to regulate transcription of many eukaryotic genes. The first of these was discovered in an upstream control region of the virus SV40 DNA... 

Because of the longer lifetime of eukaryotic messengers, it seems likely that translation level controls should play a greater role in regulation of eukaryotic gene expression. Despite this belief, few mechanisms have been elucidated. 

Eukaryotic genes may be clustered (for example, genes for a metabolic pathway may occur on the same region of a chromosome) but are independently controlled. Operons or polycistronic mRNAs do not exist in eukaryotes. This contrasts with prokaryotic genes, where a single control gene often acts on a whole cluster (for example, lac I controls the synthesis of p-galactosidase, permease, and acetylase). 

Understand the differences in the structural organization of the genomes of prokaryotes and eukaryotes and the consequences for gene control. 

The end products of gene expression are proteins, mainly enzymes, and it is essential that their levels be strictly controlled. There are many potential sites of control in both bacteria and eukaryotes. DNA or gene amplification (Chap. 16) in eukaryotes is one way of responding to the demand for more of the protein product if there arc more copies of the gene, then transcription can occur at a faster rate. More often, control is effected at the level of cither transcription or translation, with the former probably being more important for both bacteria and eukaryotes. Transcriptional control in bacteria is particularly effective because of the very short half-life (a few minutes) of mRNA in such cells the half-life is longer in eukaryotes. The prototype for transcriptional control is the lactose operon in E. coli. 

Transcriptional initiation is the most important mode for control of eukaryotic gene expression. Specific factors that exert control include the strength of promoter elements within the DNA sequences of a given gene, the presence or absence of enhancer sequences (which enhance the activity of RNA polymerase at a given promoter by binding specific transcription factors) and the interaction between multiple activator proteins and inhibitor proteins. 

The control of eukaryotic gene transcription is complicated by the fact that DNA in eukaryotic chromosomes is not bare. Instead, eukaryotic DNA is tightly bound to a group of small basic proteins called histones. In fact, histones constitute half the mass of a eukaryotic chromosome. The entire complex of a cell s DNA and associated protein is called chromatin. Five major histones are present in chromatin four histones, called H2A, H2B, H3, and H4, associate with one another the other histone is called Hi. Histones have strikingly basic properties because a quarter of the residues in each histone are either arginine or lysine. 

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