Thursday, April 9, 2009

The Role of Cis-Regulatory Sequences and Gene-Regulatory Proteins in Gene Expression

A major question in the development of vertebrates is how do genes know when to turn on during development in order to produce the right protein products that differentiate one cell type from another? Gene expression is regulated by a variety of mechanisms, from the control of transcription factors to the actual structure of the DNA itself.

The cis-regulatory control region of a gene is comprised of the sequences that flank he gene, and contain sites that can be bound by activators or repressors that can control the expression of that gene.

These control regions, in turn, can contain a variety of different cis-regulatory modules. These are short regions containing multiple binding sites for various transcription factors (e.g. activators and repressors). The combination of these factors that are bound are what determines whether a gene is switched on or off.

These activators or repressors are gnown as gene regulatory proteins, or transcription factors, that bind to control regions in DNA and help to switch genes on or off.

http://www.ucl.ac.uk/~ucbzwdr/teaching/b250-99/transcription.jpg

In addition to regulation of gene expression by transcription factors, a genes expression can also be controlled by the structure of the chromosome itself. It has been observed that if DNA is methylated (that is, has a -CH3 group bound) within a gene, transcription is downregulated. The packaging of DNA into histones also can affect gene expression, and can be modulated by transcription factors.

Histones are what DNA is wrapped around that packages it into chromatin. If a histone is acetylated by an enzyme known as histone acetyltransferases (HATs), which are usually part of large multiprotein complexes known generally as chromatin-remodeling comlexes, it tends to be more accessible to transcription. Histones can also become de-acytelated and this may play a part in gene repression.

http://journals.prous.com/journals/dof/20073201/html/df320045/images/image01.jpg

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