Regulation of gene expression in eukaryotes

   
We know about the operon systems in the bacteria and bacteriophages. The prokaryotic and eukaryotic gene systems involve a huge difference. The eukaryotic genes do not get clustered like the prokaryotic systems. The eukaryotic genes get dispersed. The exceptions include the operon systems in the nematode known as C. elegans. They consist of genes showing related functioning. The eukaryotic operons transcribe into the polycistronic mRNAs. The further processing of these molecules involves a process known as trans-splicing into monocistronic mRNAs. Hence, each gene transcript gets translated.
Transcriptionally inactive regions in the eukaryotic DNA consist of tight DNA-protein structures. Only the transcriptionally active chromosomal regions ones show looser DNA-protein structures. Hence, it helps in making the DNA sensitive to the activity of DNase I (This enzyme digests the DNA). The chromosomal regions such as the promoters show hypersensitivity to the DNase- I activity since they consist of looser DNA-protein structures. The non-expressed genes show core promoters having the chromatin structure repressive to the process of transcription. The only way to activate the process of transcription involves chromatin remodeling. It greatly involves binding of the activators to the enhancers. Without a bond between the activator and enhancer, it is not possible to carry out the remodeling smoothly. The activators mainly help in recruiting the chromatin remodeling complexes. They either involve acetylation of nucleosomes, thereby loosening their association with the DNA, or allow restructuring of the nucleosomes, thereby allowing the access of the promoters to the transcription machinery.
Both the promoter and the enhancer elements play a crucial role in the regulation of gene expression in eukaryotes. They mainly occur in the protein coding regions. The beginning or the initiation of transcription requires promoter elements. These elements are present in the core promoter. Promoter-proximal regions also have the promoter elements. These elements involve a regulatory functioning and show specializations in the genes they control. They help in the binding of the regulatory proteins involved in controlling the gene expression. Certain regulatory proteins also bind to the enhancer elements. These proteins help in the activation of transcription. Hence, both the promoter elements and the enhancer elements involve the interactions between the regulatory proteins.


Image: Regulation of gene expression in eukaryotes

The example of short-term gene regulation in the multicellular organisms includes the control of protein synthesis carried out by the hormones. The hormones activate cyclic AMP (cAMP). It acts as a secondary messenger and involves gene activity control systems. The steroid hormones show an ability to form a complex with the receptor proteins and activate them. The hormone-receptor complex then binds to a sequence in the organism’s genome for regulating the expression of specific genes. The hormone receptors are present only in specific cell types.
The transcription of a gene gets turned off due to its position in the chromosome. This process is known as gene silencing. It also involves changes in the chromatin structure leading to the production of heterochromatin. Silencing of the gene also involves methylation of cytosines in the promoter situated upstream of the gene. The phenomenon of genomic imprinting also gets associated with the methylation. It depends on the inheritance of the gene from the male or the female parent.
The level of RNA processing also involves gene expression control. The mature RNA molecules get synthesized to form the precursor RNAs through this process. The above process depends on the selection of the poly(A) site and the splice site. Another important control point involves the transport of mRNA from the nucleus to the cytoplasm. The exit of the mature mRNA requires the role of certain proteins. The spliceosomes retain the pre-RNAs in the nucleus by the signaling process. The intron removal process involves retention of the immature RNAs in the nucleus, mediated by the spliceosome signaling. After the removal of all the introns, the spliceosome complex dissociates. Now, the mature mRNA becomes free to interact with the nuclear pore complex and prepares for the exit.
Control of mRNA translation and degradation also involves regulation of gene expression. It is a major control point in the eukaryotes. Depending on the structure of the mRNAs, the degradation rates keep on fluctuating. It also depends on the role of enzymes, proteins, and cellular factors. The rate of the binding of ubiquitin to the protein determines the rate of protein breakdown.
RNA interference involves an individual mechanism of gene silencing. After cutting the double-stranded RNAs to short interfering RNAs (siRNAs), these short RNAs undergo cleavage. It results in the knockout or knockdown of the gene expression.

References:
[1] Gene Regulation, David Latchman
[2] Essentials of Genetics, Pragya Khanna
[3] Int Std Ed-General Biology, Peter Russell
[4] Fundamentals Of Molecular Biology, Veer Bala Rastogi


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