Transcription Regulatory Network
What is Transcription Regulatory Network?
Transcriptional regulation of gene expression in a cell is important to the survival and development of all organisms. For example, bacteria living in an environment of high lactose but no glucose (which is their “food source”) need to be able to alter the expression of certain genes to produce a protein that can break down lactose into glucose in order to survive and reproduce. Similarly, a cell in the human body needs to be able to respond to environmental stimuli such as harmful toxins by controlling its gene expressions so that certain proteins won’t be produced to stop the cell from moving onward to cell division. Cellular specialization of a multi-cellular organism also requires a coordinated effort of turning genes “on” and “off” at specific times so that different cells can become specialized in different ways according to the proteins they synthesize. These tasks of regulating gene transcriptions are achieved by collections of regulatory proteins and their interactions with specific sequences in the promoter regions of targeted genes. A “Transcriptional Regulatory Network” describes such regulatory proteins and interactions.
Figure: A Transcription regulatory network. (1)
Transcriptional regulatory networks in viruses and prokaryotes
Transcription regulatory proteins, often known as “activators” (activate gene transcriptions) or “repressors” (repress gene transcriptions), can be found to function in the relatively simpler genomes of viruses and prokaryokes. For example, the bacteriophage lambda alters its gene expression depending on whether it is entering the lytic cycle or the lysogenic cycle .
Although the phage lambda genome is only 48,502 base pairs long, the regulatory network that allows the phage to choose and follow one of the two cycles is quite complex already and still remains to be fully elucidated.
Figure: The phage lambda genome. (2)
Figure: The phage lambda regulatory network. (2)
For bacteria, the transcription regulatory network has been most extensively studied in E.coli. We have mentioned the need for the bacteria to metabolize lactose in the absence of glucose. In E.coli, the lac operon , a piece of DNA that contains a promoter region, an operator region and three genes, serves to regulate this process. The lac operon represents perhaps the simplest transcription regulatory mechanism; it involves a repressor protein, which is transcribed by the lacI gene and binds to the operator region, and the operator sequence itself. The presence of lactose serves to inactivate the repressor and thus allow for the transcriptions of the genes. Still, this transcription regulatory mechanism is only part of a bigger E.coli metabolic regulatory network, which may consist of as many as 149 genes, including genes that code for 16 regulatory proteins and 73 enzymes!
Figure: The transcription regulatory network for metabolism in E.coli. (3)
Transcription regulation networks in eukaryotes
As you can imagine, transcription regulatory networks in eukaryotes are even more complicated. The best-studied eukaryote model for transcriptional regulation is yeast Saccharomyces cerevisiae. Even still, for this “simple” eukaryotic organism, there are more than 200 regulatory proteins for the transcription of its >6000 genes. (4) In order to map these transcription regulation networks, a variety of experimental and computational tools are used.
Figure: An artistic rendition of the yeast gene regulatory network. (5)
Deciphering Transcription Regulatory Networks
Identifying the network participants
Coming soon
Coordination in regulation
Coming soon
Network motifs
In a transcription regulatory network, there are often recurring patterns of interactions among the regulatory proteins. These regulatory patterns are called “network motifs” (not to be confused with DNA binding motifs).
(to be continued...)
References
(1) http://genomicsgtl.energy.gov/science/generegulatorynetwork.shtml
(2) Dodd, Ian B., Shearwin, Keith E., and Egan, J. Barry. Revisited gene regulation in bacteriophage lambda. 2005. Current Opinion in Genetics & Development. 15 (2): 145-152.
(3) Covert, Markus W., and Palsson, Bernhard O. Transcriptional Regulation in Constraints-based Metabolic Models of Escherichia coli. 2002. J. Biol. Chem. 277(31): 28058-28064.
(4) Wyrick, John J., and Young, Richard A. Deciphering gene expression regulatory networks. 2002. Current Opinion in Genetics & Development. 12:130-136.
(5) http://array.mbb.yale.edu/yeast/transcription/
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