Compare and Contrast Gene Regulation in Bacteria and Human

To understand how gene regulation is controlled in both prokaryotic (Bacteria) and eukaryotic (Human) cells, we have to understand how a gene codes a functional protein in a cell. The process occurs in slightly different manners. 

Prokaryotic organisms (i.e. Bacteria) are single-cell organisms which lack a nuclear membrane, and their DNA floats freely in the cell cytoplasm. The transcription and translation processes occur simultaneously in the cytoplasm. When the resulting protein is not required, the transcription process is stopped. As a result, the fundamental method to control what type of protein and how much protein is expressed in a prokaryotic cell is the regulation of DNA transcription. When more protein is needed, more transcription occurs. Therefore, in the prokaryotic cell, the control of gene regulation is mostly at the transcriptional level.

Figure 1. Transcriptional regulation

Eukaryotic cells (i.e. Human), in contrast, have a nuclear membrane and intracellular organelles that add to their complexity. In the eukaryotic cells, to synthesize a protein, the transcription process occurs inside the cell’s nucleus. Then a new mRNA is transported out from the nucleus into the cytoplasm, where ribosomes will translate the mRNA into protein. The transcription and translation processes are physically separated by the nuclear membrane, transcription process occurs only in the cell’s nucleus and translation process occurs in the cytoplasm. The gene regulation can occur at all stages of the process. Gene regulation may occur when the DNA is uncoiled and loosened from nucleosomes to bind transcription factors (epigenetic control), when a gene is transcribed into mRNA (transcriptional control), when a mRNA is translated into protein (translational control), or when the protein has been made (post-translational control).

Figure 2. Gene regulation in eukaryotic

In general, most of the genes of prokaryotic cells (Bacteria) are set in the "switch-on" position and the main products are constantly made. In contrast, the most of genes in eukaryotic cells are set in the “switch-off”. Environmental conditions and specific protein are required before a gene can be set in the “switch-on”. The result, each eukaryotic cell has a different profile of active or inactive genes, and this is the reason for the divergence in cellular form and function in multicellular eukaryotic organisms. Not only are genes set "switch-off" and "switch-on" for specific functions, but also a cascade of gene activation and inactivation is responsible for early development and morphogenesis during ontogeny.

The DNA of eukaryotic cell is packaged with proteins (called histones) in complex known as chromatin, the basic unit of that is nucleosomes. The chromatin plays a crucial role in positive and negative gene regulation, because transcriptional activators and RNA polymerase cannot physically access the DNA regulatory elements when the chromatin is in a compact form. The DNA of prokaryotic cell, in contrast, is generally unassociated with any proteins or other structures, but it is fundamentally different from chromatin. The prokaryotic DNA can essentially be thought as naked compared to the eukaryotic chromatin which could physically interfere with gene regulation.

Figure 3. Nucleosomes

Gene regulation in prokaryotic is often organized into an operon, where two or more functionally related genes are transcribed together from a single promoter into one mRNA. The promoter of prokaryotic consists of two short sequences at -10 and -35 positions upstream from the transcription start site. The sequence at -10 is called the Pribnow box (known as the Pribnow-Schaller box), and usually consists of the six nucleotides TATAAT. The other sequence at -35 (the -35 element) usually consists of the six nucleotides TTGACA. In prokaryotic regulation, there are three types of regulatory molecules which can influence the regulation of operons, they are repressors, activators, and inducers.

Eukaryotic genomes, in contrast, do not have genes arranged in operons (except: some eukaryotes, including nematodes such as C. elegans and the fruit fly, Drosophila melanogaster) (Spieth et al., 1993; Brogna and Ashburner, 1997). One promoter common to all eukaryotic proteome genes is known as the core promoter or basal promoter. This sequence of six nucleotides TATAAA is called the TATA Box (also called the Goldberg-Hogness box) which is located 25 nucleotides away from the site at that transcription is initiated. A complex transcription factor known as IID (TFIID) binds to the TATA box by means of a TATA-binding protein (TBP). In addition to the core promoter, other cis-acting DNA sequences which regulate transcription include the proximal promoter, enhancers, silencers, and boundary/insulator elements (Butler and Kadonaga, 2002).

Prokaryotic cell has a single type of RNA polymerase which synthesizes not only mRNA but also other types of RNA. The specificity of RNA polymerase binding is mediated by sigma factors. Eukaryotic cells, in contrast, have three different RNA polymerases, they are RNA polymerase I, RNA polymerase II, and RNA polymerase III which responsible for transcribing certain types of genes. The proteome is transcribed by RNA polymerase II which has factors involved in the accurate transcription that can be classified into three groups: general transcription factors (GTFs), promoter-specific activator proteins (activators), and coactivators (Matson, et al., 2006).

Prokaryotic mRNAs are polycistronic, containing multiple ribosome-binding sites located near the start sites for all the protein-coding regions in the mRNA. As a consequence, translation initiation can begin at internal sites in a polycistronic mRNA molecule, and produce multiple proteins. The most mRNAs of eukaryotic are monocistronic. Most of transcription units yield mRNAs which encode only one protein. This difference correlates with a fundamental contrast in mRNA translation in prokaryotes and eukaryotes.

Another difference between prokaryotic and eukaryotic gene regulation is in the step after transcription (post-transcriptional control). In the eukaryotic, a pre-mRNA should be properly modified by the covalent attachment of a 7-methylguanylate, called 5′ cap, splicing out of non-coding protein “introns”, leaving just the protein-coding exons in the final mRNA, and addition of the 3′ poly-A tail. Each of these processing steps must be properly completed, if any of them are not properly completed, the mRNA will be degraded. The transport out mechanism of mRNA from the nucleus to the cytoplasm is also regulated, as the stability of the properly processed mRNA in the cytoplasm.

In general, the gene regulation of eukaryotic is more complex than the gene regulation of prokaryotic. Yet many of them are in the same principles: positive transcription regulators (activators) help RNA polymerase begin transcribing genes, and negative regulators (repressors) block this from happening (Prokaryotic: activator and repressor proteins act on operators. Eukaryotic: activator proteins act on enhancer DNA sequences; repressor proteins act on silencer DNA sequences). In prokaryotes, most of the interactions between DNA-bound transcription regulators and RNA polymerase (whether activate or repress transcription) are direct. Eukaryotes, in contrast, these interactions are almost always indirect, many intermediate proteins, including the histones, act between the DNA-bound transcription regulator and RNA polymerase. 

References:

1. Alberts, Bruce, A. Johnson, J. Lewis, D. Morgan, M. Raff, K. Roberts, and P. Walter. 2014. Molecular Biology of The Cell. 6th Edition. New York: Garland Science, Taylor & Francis Group, LLC.
2. Brogna, S. and M. Ashburner. (1997). The Adh-related Gene of Drosophila melanogaster is Expressed as a Functional Dicistronic messenger RNA: Multigenic Transcription in Higher Organisms. The EMBO Journal. 16 (8): 2023–2031. 
3. Butler, Jennifer E.F. and J.T. Kadonaga. 2002. The RNA Polymerase II Core Promoter: A Key Component in The Regulation of Gene Expression. GENES & DEVELOPMENT 16:2583–2592.
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5. Matson, G.A., Evans, K.E., and Green, M.R. 2006. Transcriptional Regulatory Elements in the Human Genome. Annu. Rev. Genomics Hum. Genet. 7:29–59. 
6. Spieth, J.; Brooke, G.; Kuersten, S.; Lea, K.; Blumenthal, T. (1993). Operons in C. Elegans: polycistronic mRNA precursors are processed by trans-splicing of SL2 to downstream coding regions. Cell. 73 (3): 521–532.