Gene Regulation

Gene regulation refers to a broad range of mechanisms that cells use to control genes to be expressed in their DNA and further to make a functional product such as a protein. Cells respond and adapt to environmental signals by turning on or off the expression of appropriate genes. Gene expression is the process through which structural genes are directed to protein synthesis. Real-time quantitative (RT-PCR), in situ hybridization, microarrays, and massively parallel signature sequencing are some of the technologies used for detecting the expressed genes. All cells in a multicellular organism contain the same DNA but they have a different set of active genes, which gives each cell a unique specialization to perform its function. Gene regulation can occur at various steps-

• Transcriptional control
• Translational control
• Post-translational control

All these three steps of regulating gene expression use positive, negative, and co-regulation. Transcription is the primary step of DNA based gene expression which uses information from a gene to make a protein. RNA polymerase binds to certain sites in the DNA known as the promoter. Transcription factors are regulatory proteins characterized by conserved structural motifs that regulate the transcription of genes by binding to the promoter. Regulatory elements either help in recruiting or repelling RNA polymerase on these factors. They control the transcription process in a positive or negative way. Transcriptional regulation orchestrates gene activity and is based on modular construction of cis-elements and combinatory control by trans-elements. Cis-acting elements and trans-acting factors together make a translation initiation complex. Cis-elements are the DNA sequences located in the vicinity of the structural portion of a gene that affects the level of transcription including core-promoters, distal promoters, enhancers, and operators. Trans-elements are DNA-binding proteins that are responsible for changing the level of transcription such as transcriptional activators or repressors. Core promoter and promoter-proximal elements are both responsible for binding RNA-polymerase II to bind with its promoter. Distance-independent cis-acting elements such as enhancers and silencers have the ability to induce and repress the transcription process by operating either upstream or downstream from the promoter. Specific transcriptional regulatory proteins are bound to enhancers that work together to regulate gene expression during development and differentiation. DNA Footprinting and electrophoretic-mobility shift assay are the experiments used for analyzing transcriptional regulatory proteins. Repressors inhibit the expression of tissue-specific genes in inappropriate cell types via protein-protein interactions. DNA is packaged into chromatin which together with a repeating unit of histones forms a nucleosome. DNA needs to be unwrapped from the histone core for binding to the transcription factors thus, histone modification through acetylation and methylation, followed by phosphorylation is responsible for intricate gene regulation. Nucleosome remodeling factors alter the nucleosome structure thus increasing the accessibility of nucleosomal DNA and further facilitating the binding of transcription factors to chromatin. The methylation of DNA is another general mechanism capable of inhibiting transcription. microRNAs are the small regulatory RNAs targets and inhibit protein expression from specific mRNAs and are responsible for controlling mRNA lifespan and translation. Ribosomes assemble on the mRNA to begin the translation process which requires the involvement of a protein called eukaryotic initiation factor-2 (eIF-2). Phosphorylation of this factor can inhibit the translation process. Some of the common post-translational modifications are phosphorylation and ubiquitination for controlling the persistence of a protein in the cell.

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