Cis & Trans Regulatory Elements, Research Paper Example

Introduction

Gene’s store and control specific information for all life forms and each species has a specific DNA (De-oxy Ribose Nucleic Acid) which determines its characteristics. Genomics is the science which describes the regulatory mechanisms of gene expression. One of the key steps in gene regulation is the binding of the transcription factors (trans-elements) to their DNA recognition sites (cis elements) which is highly sequence specific (Folter & Angenent, 2006). Besides the cis–trans interaction, the expression patterns of down-stream target genes can additionally under control by spatial and temporal expression of transcription factor genes. This aids in the control of distinct biological processes by transcription factors with similar DNA binding properties.

A typical gene contains a transcriptional region and a regulatory region. Transcriptional region of DNA contains the information to be transcribed into a primary transcript which is usually an RNA (Ribose Nucleic Acid) molecule which is complimentary to the transcriptional region of the DNA. The regulatory region of the DNA is divided into cis-regulatory and trans-regulatory elements which determine gene expression. The cis-regulatory elements act as binding sites for specific proteins known as the transcription factors which either inhibit or enhance the transcription process. The trans-regulatory elements, on the other hand, are composed of DNA sequences which encode transcription factors. The cis-regulatory elements are usually present on the same strand of the gene which they regulate while trans-regulatory elements can regulate other genes distant from its primary location as well.

The cis-regulatory elements, depending upon their functional characteristics, can be categorized as promoter, enhancer, silencer and response elements. Promoter is that element from where the transcription initiation occurs. An enhancer element serves the functional basis it is named after i.e. it enhances transcription upon binding with transcription factors under the stimulus of additional factors known as transcriptional activators. The role of the silencer is to repress transcription with assistance from transcription factors known as repressors. The response element is the recognition site of transcription factors. Cis-acting elements are the DNA sequences within the vicinity of a structural component of gene which are required for gene expression while the trans-acting factors are proteins which bind to the cis-acting sequences for a control of gene expression. Trans acting factors are subunits of RNA polymerase and bind with this enzyme to stabilize the initiation complex. They also bind to promoters at specific sequences during transcription.

Gene expression profiles in all species can maintain their purity across large evolutionary distances and any phenotype variation that occurs is due to changes in gene expression directed by transcriptional regulators (Wilson & Odom, 2009). The exploration of interaction of mammalian transcription factors with DNA is currently an intensive area of research which tries to elucidate many mechanisms of normal as well as abnormal replication during disease processes. The cis and trans regulation of gene expression is one of the primary focus areas of current research.   Genetic differences across species are responsible for variability of gene expression which has been studied by well established mechanisms for identifying cis-acting polymorphisms (Sladek & Hudson, 2006). However trans effects still pose a challenge as they have minor individual effects which are difficult to observe and evaluate under experimental conditions. Gene expression divergence is subject to both cis and trans regulatory mutations as well as polymorphisms (Thompson & Regev, 2009). In cis regulation, any genetic change can directly influence gene expression directly by altering the TF binding sites in the promoter region. This results either in a change in chromatin organization, or destabilization of mRNA (messenger RNA). cis regulation can also affect expression indirectly by modifying activity of the gene product resulting in expression changes by feed-back control. In trans regulation, polymorphism in one gene can affect expression in other genes as well.

Regulatory divergence is considered as a vital factor in evolution. Comparative genomics is a useful tool for molecular biologists to study the evolution of gene regulation. Recent advances in the identification of the contribution of cis- and trans-factors to expression divergence have yielded vital information about the mechanisms of gene expression.

References

Folter, S. de, & Angenent, G. C. (2006). Trans meets cis in mads science. Trends in Plant Science, 11(5), 224-231.

Sladek, R. & Hudson, T. J. (2006). Elucidating cis- and trans-regulatory variation using genetical genomics. Trends in Genetics, 22(5), 245-250.

Thompson, D. A. & Regev, A. (2009). Fungal regulatory evolution: cis and trans in the balance. FEBS Letters xxx, Article in print.

Wilson, M. D., & Odom, D. T. (2009). Evolution of transcriptional control in mammals, In press. Current Opinion in Genetics & Development, 19, 1-7.