Thursday, February 07, 2008

Regulation of Transcription

From Horton et al. (2006), pp. 663-665.

Many genes are expressed in every cell. The expression of these housekeeping genes is said to be constitutive. In general, such genes have strong promoters and are transcribed efficiently and continuously. Genes whose products are required at low levels usually have weak promoters and are transcribed infrequently. In addition to constitutively expressed genes, cells contain genes that are expressed at high levels in some circumstances and not at all in others. Such genes are said to be regulated.

Regulation of gene expression can occur at any point in the flow of biological information but occurs most often at the level of transcription. Various mechanisms have evolved that allow cells to program gene expression during differentiation and development and to respond to environmental stimuli.

The initiation of transcription of regulated genes is controlled by regulatory proteins that bind to specific DNA sequences. Transcriptional regulation can be negative or positive. Transcription of a negatively regulated gene is prevented by a regulatory protein called a repressor. A negatively regulated gene can be transcribed only in the absence of active repressor. Transcription of a positively regulated gene can be activated by a regulatory protein called an activator. A positively regulated gene is transcribed poorly or not at all in the absence of the activator.

Repressors and activators are often allosteric proteins whose function is modified by ligand binding. In general, a ligand alters the conformation of the protein and affects its ability to bind to specific DNA sequences. For example, some repressors control the synthesis of enzymes for a catabolic pathway. In the absence of substrate for these enzymes, the genes are repressed. When substrate is present, it binds to the repressor, causing the repressor to dissociate from the DNA and allowing the genes to be transcribed. Ligands that bind to and inactivate repressors are called inducers because they induce transcription of the genes controlled by the repressors. In contrast, some repressors that control the synthesis of enzymes for a biosynthetic pathway bind to DNA only when associated with a ligand. The ligand is often the end product of the biosynthetic pathway. This regulatory mechanism ensures that the genes are turned off as product accumulates. Ligands that bind to and activate repressors are called corepressors. The DNA-binding activity of allosteric activators can also be affected in two ways by ligand binding. Four general strategies for regulating transcription are illustrated in the figures. Examples of all four strategies have been identified.

Few regulatory systems are as simple as those described above. For example, the transcription of many genes is regulated by a combination of repressors and activators or by multiple activators. Elaborate mechanisms for regulating transcription have evolved to meet the specific requirements of individual organisms. When transcription is regulated by a host of mechanisms acting together, a greater range of cellular responses is possible. By examining how the transcription of a few particular genes is controlled, we can begin to understand how positive and negative mechanisms can be combined to produce the remarkably sensitive regulation seen in bacterial cells.

©Laurence A. Moran and Pearson Prentice Hall

Horton, H.R., Moran, L.A., Scrimgeour, K.G., perry, M.D. and Rawn, J.D. (2006) Principles of Biochemisty. Pearson/Preintic Hall, Upper Saddle River N.J. (USA)

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