Question

There are many things that differentiate the structure and function of prokaryotes compared to eukaryotes. Summarize the process of eukaryotic gene regulation and explain why this process if different from the operon model of gene regulation in prokaryotes.

Answer 1

Let us look at the basics of gene regulation. It basically means controlling which genes in DNA will be expressed (genes expressed means which genes are 'turned on') to do a particular function like the formation of a particular protein. A different set of genes may be present in the same DNA. If genes are different, RNA and proteins encoded by them will be different, giving the cell its unique properties. In eukaryotes, the gene can be regulated at multiple steps of gene expression, the most common one being transcription.

How to decide which genes will be turned on? It depends on many factors,

• factors outside the cell e.g. certain chemical signals produced by different cells
• factors within the cell e.g. inherited proteins

Let us understand step by step through an example (we will consider growth factor as a chemical signal). The following steps in gene regulation can be summarized as follows,

• recognition of growth factor by its physical binding with the cell receptor protein
• receptor changes shape and activates transcription factors in the cell
• binding of transcription factors to DNA causing transcription of genes responsible for cell division (as the signal is a growth factor)
• transcription is followed by translation leading to the formation of various kinds of proteins useful for cell division.

Various stages at which gene expression can be regulated can be summarized as follows:

1. At the level of chromatin structure (epigenetic level): open chromatin (uncoiling of consed chromatin) facilitates transcription.
2. At the level of transcription: Certain transcription factors bind to specific DNA sequences. They can promote or suppress its transcription into RNA.
3. At the level of RNA processing: Various processes such as the addition of poly-A tail, splicing, capping, etc. can be regulated. The exit of RNA from the nucleus can also be regulated.
4. At the level of the process causing RNA stability: The amount of time mRNA stays in the cytoplasm determines how many proteins can be made from it. There is something called miRNA which is a small regulatory RNA that can chop the mRNA.
5. At the level of translation: Translation can be inhibited or increased by the regulators. miRNAs (as mentioned earlier) can also block translation rather than chopping them up.
6. At the level of protein activity: Proteins formed by translation can undergo post-translational modifications such as breaking up or getting tagged with certain chemical groups. These modifications can be regulated that can further alter the behavior and function of proteins.  

Among all these steps, transcription is the main controlling point for many genes.

Now, coming to answering the second part i.e., the difference of gene regulation in eukaryotes and prokaryotes. Prokaryotes lack nucleus and DNA is found in the cytoplasm as opposed to eukaryotes. In prokaryotes, transcription and translation occur simultaneously as there is no nuclear membrane separating the processes. Gene expression is regulated primarily at the transcriptional level in prokaryotes while in eukaryotes it is controlled at many levels as explained above.

DNA of prokaryotes have circular chromosomes. Proteins that are required for specific functions are encoded in blocks called operons e.g., lactose operon. The genes are transcribed together under the control of one promotor which controls all genes at one particular time (like all or none phenomenon). There are 3 types of regulatory molecules affecting operon expression.

• Repressors: In presence of an external stimulus, these proteins suppress gene transcription.
• Activators: In presence of an external stimulus, these molecules activate or increase the transcription of a gene.
• Inducers: These are small molecules that can either activate or suppress the process of transcription. It depends upon the cell requirement and substrate availability.