How are genes coordinately controlled in eukaryotic cells?

Welcome back, Rakesh,

Gene regulation is a fascinating area of genetics. Gene regulation lies at the heart of questions such as how an E. coli cell can grow and live on different carbon sources, or how a single fertilized human egg can develop into all of the tissues (e.g., muscle, liver, heart, etc.) of an adult human. To get at the answer to your question about the differences between prokaryotic and eukaryotic gene regulation, we will also point out some of the similarities between these important processes. Please keep in mind that our answers are generalized – there are always exceptions to any rule!

Gene regulation can occur at any step along the path of gene expression. That is, gene regulation can happen at any stage in the pathway from DNA to RNA to protein. Many genes in both prokaryotes and eukaryotes regulate their expression at the step of transcription, the DNA to RNA step in the pathway. This might make sense because both transcription and translation (the RNA to protein step in the pathway) are energetically expensive processes. The cell can save resources by not making RNA for a protein it doesn’t need.

To regulate transcription, both prokaryotes and eukaryotes rely on proteins that act as either activators that “turn on” gene expression or repressors that “turn off” gene expression. Repressors are more common in prokaryotes than they are in eukaryotes. This might make sense to you if you consider the number of genes in each type of organism; prokaryotes have fewer genes, so it is easier to turn off those not needed, while eukaryotes have more genes, so they tend to turn on the genes that they need.

Prokaryotes also regulate genes through the use of operons. Operons are a set of genes that lie near one another on the chromosome, and they are coordinately transcribed so that these genes are turned on or turned off together. In this way, prokaryotes can, for example, turn on all of the genes needed to perform a particular function, such as those needed to make a particular amino acid when their environment lacks that nutrient. Eukaryotes can coordinate gene expression too, but it is usually done in much different ways. For example, when a eukaryotic cell must respond to a hormone, such as glucocorticoid, the hormone binds an intracellular receptor and the hormone-receptor complex can bind to DNA sequences called “response elements.” The binding of the hormone-receptor complex to a response element turns on any gene that has those elements. All of the genes that must respond to the glucocorticoid have the same response element, allowing many genes to be turned on at once.

Even though much of the gene regulation in prokaryotes and eukaryotes occurs at the level of transcription, as we mentioned earlier, gene regulation can occur at ANY stage of the process from DNA to RNA to protein. For example, an mRNA may be transcribed, but not translated, either because the mRNA was degraded before it could be translated, or because a regulatory protein blocked the translation of the mRNA. In prokaryotes, both transcription and translation may be coordinately regulated because they occur in the same space, but in eukaryotes, the location of transcription and translation are separated by the nuclear envelope.

Eukaryotes regulate their genes at many steps in the pathway from DNA to RNA to protein that do not typically occur in prokaryotes or in ways that are not available to prokaryotes. For example, eukaryotic DNA exists in protein complexes called chromatin. One of the key classes of proteins in chromatin is called histones, which are proteins that help pack the DNA. The histone proteins can be modified by the addition of chemical groups such as acetyl groups or methyl groups, and the degree of acetylation or methylation of the histones loosens or tightens the packing of the DNA. In eukaryotes, there are regulatory proteins that control the modification of the histones, and hence the tightness of the DNA packing. When DNA is tightly packed, it cannot be transcribed. An ever-growing number of researchers are now studying the effects of the chemical modification of DNA directly, rather than through the modification of the proteins the DNA interacts with. This is an exciting field of epigenetics, and there is growing evidence that these epigenetic tags effect gene expression in both prokaryotes and eukaryotes.

Another example of a step in gene expression that can be regulated in eukaryotes, but not in prokaryotes, is mRNA processing. Eukaryotic mRNA is modified before it is translated such that a 5’ cap and poly-A tail are added and introns are spliced out to form the mature mRNA. All of these processes can be regulated in eukaryotes. Once the mRNA is made in eukaryotes, it must then be transported to the cytoplasm for translation. This transport step may also be regulated.

We hope the information we’ve provided has helped to expand your knowledge of some differences between prokaryotic and eukaryotic gene regulation. And we’d also like to encourage you to consider a couple of intriguing aspects of eukaryotic gene regulation. Notably, although the regulation of gene expression in eukaryotes is often dynamic and ever-changing, it can also occur on a long-term basis. For example, a form of hemoglobin used in human embryos can be permanently turned off in adult cells. Furthermore, tissue-specific genes expression occurs in eukaryotes, but not in prokaryotes. You might also be interested in learning more about the topics of non-coding RNAs, RNA interference (RNAi), and microRNAs, which play key roles in gene regulation. We’ve provided you with a collection of links to helpful websites that cover these fascinating topics. Happy reading!

To learn more, visit the Gene Expression and Regulation topic room here at Scitable. It has a great collection of articles full of information on this fascinating subject:
http://www.nature.com/scitable/topic/gene-expression-and-regulation-15

To learn more about histone modifications, see these links:
http://www.nature.com/scitable/topicpage/chromatin-remodeling-in-eukaryotes-1082
http://www.nature.com/scitable/content/reading-signals-on-the-nucleosome-with-a-16846
http://jhc.sagepub.com/content/56/8/711.full
http://www.ncbi.nlm.nih.gov/books/NBK45032/#_ch4689_s6_
http://www.nature.com/scitable/content/the-language-of-covalent-histone-modifications-17157
http://www.nature.com/scitable/topicpage/examining-histone-modifications-with-chromatin-immunoprecipitation-and-1050

To read about non-coding mRNAs, RNAi, and microRNAs, follow these links:
http://www.nature.com/scitable/topicpage/small-non-coding-rna-and-gene-expression-1078
http://www.nature.com/scitable/topicpage/Some-Sections-of-DNA-Do-Not-Determine-6525008
http://www.nature.com/scitable/topicpage/transposons-or-jumping-genes-not-junk-dna-1211
http://www.npr.org/2011/08/19/139757702/dont-throw-it-out-junk-dna-essential-in-evolution

For information about epigenetics, follow these links:
http://www.nature.com/scitable/spotlight/epigenetics-26097411
http://learn.genetics.utah.edu/content/epigenetics/
http://www.ncbi.nlm.nih.gov/books/NBK45032/
http://www.nature.com/scitable/topicpage/Obesity-Epigenetics-and-Gene-Regulation-927
http://www.nature.com/scitable/topicpage/Epigenetic-Influences-and-Disease-895
http://mmbr.asm.org/content/70/3/830.full

How gene expression is controlled in prokaryotes and eukaryotes?

Prokaryotic gene expression is primarily controlled at the level of transcription. Eukaryotic gene expression is controlled at the levels of epigenetics, transcription, post-transcription, translation, and post-translation.

How most eukaryotic genes are controlled?

Most eukaryotic genes are controlled at the level of transcription by proteins (trans-acting factors) that interact with specific gene sequences (cis-acting regulatory sequences).

How do introns regulate genes?

Introns can increase transcript levels by affecting the rate of transcription, nuclear export, and transcript stability. Moreover, introns can also increase the efficiency of mRNA translation.

How is transcription directly controlled in eukaryotic cells?

Regulation of transcription in eukaryotes is a result of the combined effects of structural properties (how DNA is "packaged") and the interactions of proteins called transcription factors. The most important structural difference between eukaryotic and prokaryotic DNA is the formation of chromatin in eukaryotes.