Overview: Eukaryotic gene regulation
How different genes are expressed in different cell types. The big picture of eukaryotic gene regulation.
- Gene regulation is the process of controlling which genes in a cell's DNA are expressed (used to make a functional product such as a protein).
- Different cells in a multicellular organism may express very different sets of genes, even though they contain the same DNA.
- The set of genes expressed in a cell determines the set of proteins and functional RNAs it contains, giving it its unique properties.
- In eukaryotes like humans, gene expression involves many steps, and gene regulation can occur at any of these steps. However, many genes are regulated primarily at the level of transcription.
Your amazing body contains hundreds of different cell types, from immune cells to skin cells to neurons. Almost all of your cells contain the same set of DNA instructions – so why do they look so different, and do such different jobs? The answer: different gene regulation!
Gene regulation makes cells different
Gene regulation is how a cell controls which genes, out of the many genes in its genome, are "turned on" (expressed). Thanks to gene regulation, each cell type in your body has a different set of active genes – despite the fact that almost all the cells of your body contain the exact same DNA. These different patterns of gene expression cause your various cell types to have different sets of proteins, making each cell type uniquely specialized to do its job.
For example, one of the jobs of the liver is to remove toxic substances like alcohol from the bloodstream. To do this, liver cells express genes encoding subunits (pieces) of an enzyme called alcohol dehydrogenase. This enzyme breaks alcohol down into a non-toxic molecule. The neurons in a person's brain don’t remove toxins from the body, so they keep these genes unexpressed, or “turned off.” Similarly, the cells of the liver don’t send signals using neurotransmitters, so they keep neurotransmitter genes turned off.
Left panel: liver cell. The liver cell contains alcohol dehydrogenase proteins. If we look in the nucleus, we see that an alcohol dehydrogenase gene is expressed to make RNA, while a neurotransmitter gene is not. The RNA is processed and translated, which is why the alcohol dehydrogenase proteins are found in the cell.
Right panel: neuron. The neuron contains neurotransmitter proteins. If we look in the nucleus, we see that the alcohol dehydrogenase gene is not expressed to make RNA, while the neurotransmitter gene is. The RNA is processed and translated, which is why the neurotransmitter proteins are found in the cell.
There are many other genes that are expressed differently between liver cells and neurons (or any two cell types in a multicellular organism like yourself).
How do cells "decide" which genes to turn on?
Now there's a tricky question! Many factors can affect which genes a cell expresses. Different cell types express different sets of genes, as we saw above. However, two different cells of the same type may also have different gene expression patterns depending on their environment and internal state.
Broadly speaking, we can say that a cell's gene expression pattern is determined by information from both inside and outside the cell.
- Examples of information from inside the cell: the proteins it inherited from its mother cell, whether its DNA is damaged, and how much ATP it has.
- Examples of information from outside the cell: chemical signals from other cells, mechanical signals from the extracellular matrix, and nutrient levels.
How do these cues help a cell "decide" what genes to express? Cells don't make decisions in the sense that you or I would. Instead, they have molecular pathways that convert information – such as the binding of a chemical signal to its receptor – into a change in gene expression.
As an example, let's consider how cells respond to growth factors. A growth factor is a chemical signal from a neighboring cell that instructs a target cell to grow and divide. We could say that the cell "notices" the growth factor and "decides" to divide, but how do these processes actually occur?
Growth factors bind to their receptors on the cell surface and activate a signaling pathway in the cell. The signaling pathway activates transcription factors in the nucleus, which bind to DNA near division-promoting and growth-promoting genes and cause them to be transcribed into RNA. The RNA is processed and exported from the nucleus, then translated to make proteins that drive growth and division.
- The cell detects the growth factor through physical binding of the growth factor to a receptor protein on the cell surface.
- Binding of the growth factor causes the receptor to change shape, triggering a series of chemical events in the cell that activate proteins called transcription factors.
- The transcription factors bind to certain sequences of DNA in the nucleus and cause transcription of cell division-related genes.
- The products of these genes are various types of proteins that make the cell divide (drive cell growth and/or push the cell forward in the cell cycle).
This is just one example of how a cell can convert a source of information into a change in gene expression. There are many others, and understanding the logic of gene regulation is an area of ongoing research in biology today.
Growth factor signaling is complex and involves the activation of a variety of targets, including both transcription factors and non-transcription factor proteins. You can learn more about how growth factor signaling works in the article on intracellular signal transduction.
Eukaryotic gene expression can be regulated at many stages
In the articles that follow, we’ll examine different forms of eukaryotic gene regulation. That is, we'll see how the expression of genes in eukaryotes (like us!) can be controlled at various stages, from the availability of DNA to the production of mRNAs to the translation and processing of proteins.
Eukaryotic gene expression involves many steps, and almost all of them can be regulated. Different genes are regulated at different points, and it’s not uncommon for a gene (particularly an important or powerful one) to be regulated at multiple steps.
- Chromatin accessibility. The structure of chromatin (DNA and its organizing proteins) can be regulated. More open or “relaxed” chromatin makes a gene more available for transcription.
- Transcription. Transcription is a key regulatory point for many genes. Sets of transcription factor proteins bind to specific DNA sequences in or near a gene and promote or repress its transcription into an RNA.
- RNA processing. Splicing, capping, and addition of a poly-A tail to an RNA molecule can be regulated, and so can exit from the nucleus. Different mRNAs may be made from the same pre-mRNA by alternative splicing.
Stages of eukaryotic gene expression (any of which can be potentially regulated).
- Chromatin structure. Chromatin may be tightly compacted or loose and open.
- Transcription. An available gene (with sufficiently open chromatin) is transcribed to make a primary transcript.
- Processing and export. The primary transcript is processed (spliced, capped, given a poly-A tail) and shipped out of the nucleus.
- mRNA stability. In the cytosol, the mRNA may be stable for long periods of time or may be quickly degraded (broken down).
- Translation. The mRNA may be translated more or less readily/frequently by ribosomes to make a polypeptide.
- Protein processing. The polypeptide may undergo various types of processing, including proteolytic cleavage (snipping off of amino acids) and addition of chemical modifications, such as phosphate groups.
All these steps (if applicable) need to be executed for a given gene for an active protein to be present in the cell.
- RNA stability. The lifetime of an mRNA molecule in the cytosol affects how many proteins can be made from it. Small regulatory RNAs called miRNAs can bind to target mRNAs and cause them to be chopped up.
- Translation. Translation of an mRNA may be increased or inhibited by regulators. For instance, miRNAs sometimes block translation of their target mRNAs (rather than causing them to be chopped up).
- Protein activity. Proteins can undergo a variety of modifications, such as being chopped up or tagged with chemical groups. These modifications can be regulated and may affect the activity or behavior of the protein.
Although all stages of gene expression can be regulated, the main control point for many genes is transcription. Later stages of regulation often refine the gene expression patterns that are "roughed out" during transcription.
To learn more, see the articles on transcription factors and regulation after transcription.
Gene regulation and differences between species
Differences in gene regulation makes the different cell types in a multicellular organism (such as yourself) unique in structure and function. If we zoom out a step, gene regulation can also help us explain some of the differences in form and function between different species with relatively similar gene sequences.
For instance, humans and chimpanzees have genomes that are about identical at the DNA level. The protein-coding sequences of some genes are different between humans and chimpanzees, contributing to the differences between the species. However, researchers also think that changes in gene regulation play a major role in making humans and chimps different from one another. For instance, some DNA regions that are present in the chimpanzee genome but missing in the human genome contain known gene-regulatory sequences that control when, where, or how strongly a gene is expressed.
Want to join the conversation?
- Can any one explain it to me ?!
"Later stages of regulation often refine the gene expression patterns that are "roughed out" during transcription."(5 votes)
- what is the difference between Eukaryotic gene regulation and Prokaroytic gene regulation(4 votes)
- The two major differences have to do with the fact that there is no nucleus in prokaryotes and it is linear DNA.(3 votes)
- I am confused about gene regulation in each process. I want to know how replication, transcription, and translation are regulated in eukaryotes. Can you explain it?(5 votes)
- When it says that "almost all cells have the exact same DNA", does that mean that some cells have different DNA than the rest of the body? (are they talking about sex cells?)(1 vote)
- Yes that is one example. Another would be red blood cells, when they are mature they no longer have a nucleus. Also in some immune cells, DNA is modified to make more variety so you can have lots of different antibodies. But in that case, only very small region of DNA is changed - most genes are left the same. Maybe there are a few more exceptions, but most cells have the same DNA.(4 votes)
- two exambles of epigenetic effects that control gene expression in eukaryotic cells(2 votes)
- Epigenetic inactivation of the X chromosome in females - from pharmaceuticals.
Honeybees are genetically identical but queen bees can produce as many as 2,000 eggs in a single day, whereas worker bees are sterile.(2 votes)
- how are euchromatin and heterochromatin in a fat cell after a fat meal as compared to dieting?(2 votes)
- I don't think euchromatin and heterochromatin influence adipose tissue in terms of dieting.
However, there is Interleukin signaling ina adipose tissue which affects brown tissue (thermogenesis and
There is a paper where it is showed that High-Fat diet affects and lowers activity of deacetylation (histone modification) but only in Pancreas not in Liver.
- What are Regulatory Mechanisms in relation to Gene Expression?(2 votes)
- Is this the same or related to epigenetics?(1 vote)
- Epigenetics refers to changes that can be inherited by daughter cells (and sometimes even offspring), but don't involve changing the sequence of the DNA.
These changes typically involve alterations in chromatin accessibility, but some alterations in chromatin accessibility are not heritable (and thus aren't epigenetic).
So, I would classify epigenetics as one type of gene regulation.
Khan Academy has more material on this, which can be found by entering "epigenetics" into the search field found near the top of every page — this will lead you to these results:
Some additional resources for learning more:
• https://en.wikipedia.org/wiki/Epigenetics(2 votes)
- Someone right me a summary(1 vote)
- It is just repeating things that were in the earlier articles and videos in the Regulation of Gene Expression and Cell Specialization. I just skimmed it.(1 vote)
- How is translation regulated? Like how do ribosomes "know" when to read mRNA and when not to. What does an example of this feedback loop look like.(1 vote)