Eukaryotic Gene Regulation

Key Points
1. GR- the process of controlling which genes in a cell's DNA are expressed.
  1. Used to make a functional product; such as a protein.
2. Different cells in multicellular organisms may express very different sets of genes, even though they contain the same DNA
3. The set of genes expressed in a celldetermines the set of proteins and functional RNAs it contains.
  1. This gives it it's unique properties
4. In eukaryotes, like humans, gene expression involves many steps, and gene regulation can occur at any of these steps.
  1. However, many genes are regulated primarily at the level of transcription.
Gene regulation makes cells different.
1. GR is how a cell controls which of it's many genes, within it's genome are "turned on" (expressed).
  1. Due to GR each cell type within the body has a different set of active genes.
    1. Despite the fact that almost all the cells in your body contain the exact same DNA
      1. These different patterns of gene expression cause your various cell types to have different sets of proteins, making each cell uniquely specialized to do it's job
        For example, one of the jobs of the live is to remove toxic substances like alcohol from the bloodstream. To do this, liver cells express genes encoding subunits 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.
        Similarly the cells of the liver don't send signals using neurotransmitters, so they keep their neurotransmitter genes unexpressed.
        There are many other genes that are ezpressed differently between liver cells and neurones (or any two cell types in a multicellular organism like yourself)
How do cells "decide" which genes to turn on?
1. Many factors that can affect which genes a cell expresses.
  1. Different cell types express different sets of genes. However, two different cells of the same type may also have different gene expression patterns depending on their environment and internal state.
2. A cell's gene expression pattern is determined by information from both inside and outside the cell.
  1. Examples of information inside the cell: the proteins it inherited from it's mother cell, whether its DNA is damaged, and how much ATP it has.
  2. Examples of information outside the cell: chemical signals from other cells, mechanical signals from the extracellular matrix, and nutrient levels.
3. Cells have molecular pathways that convert information - such as the binding of a chemical signal to its receptor - into a change in gene expression.
  1. E.G - A growth factor is a chemical signal from a neighboring cell that instructs a target cell to grow and divide. The cell "notices" the growth factor and "decides" to divide.
    1. The cell detects the growth factor through physical binding of the growth factor to a receptor protein on the cell surface.
      1. 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. (Drice cell growth and/or push the cell forward in the cell cycle)
4. Growth factor signalling is complex and involves the activation of a variety of targets, including both transcription factors and non-transcription factor proteins.
Gene expression can be regulated at many stages
1. Gene expression involves many steps and almost all of them can be regulated.
  1. 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.
  2. Transcription - 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
  3. 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.
  4. 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.
  5. 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)
  6. 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.
2. 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.
Bacterial Gene Regulation
1. Key Points
  1. Bacterial genes are often found in operon. Genes in an operon are transcribed as a group and have a single promoter.
  2. Each operon contains regulatory DNA sequences, which act as binding sites for regulatory proteins that promote or inhibit transcription.
  3. Regulatory proteins often bind to small molecules, which can make the protein active or inactive by changing its ability to bind to DNA.
  4. Some operons are inducible, meaning they cn be turned on by the presence of a particular small molecule. Others are repressible, meaning that they are on by default but can be turned off by a small molecule.
2. Introduction
  1. The bacteria in your gut or between your teeth have genomes that contain thousands of different genes. Mos of these gense encode proteins, each with its own role in a process such as fuelling metabolism, maintenance of cell structure, and defense against viruses.
  2. Some of these proteins are needed routinely, while others are needed only under certain circumstances. Thus, cells don't express all the genes in their genome all the time.
    1. You can think of the genome as being like a cookbook with many different recipes in it. The cell will only use the recipes (express the genes) that fit its current needs.
3. How is Gene Expression regulated?
  1. There are various forms of gene regulation, that is, mechanisms for controlling which genes get expressed and at what levels. However, a lot of gene regulation occurs at the level of transcription
  2. Bacteria have specific regulatory molecules that control whether a particular gene will be transcribed into mRNA.
    1. Often, these molecules act by binding to DNA near the gene and helping or blocking the transcription enzyme, RNA polymerase.
4. In bacteria. genes are found in Operons.
  1. Related genes are often found in a cluster on the chromosome where the are transcribed from one promoter (RNA Polymerase binding site) as a single unit. Such a cluster of genes is under control of a single promoter known as an operon.
    1. Operons are common in bacteria, but they are rare in eukaryotes, such as humans.
  2. In general, an operon will contain genes than function in the same process.
    1. For example, a well studied operon called the lac operon contains genes that encode proteins involved in uptake and metabolism of a particular sugar, lactose..
      1. Operons allow the cell to efficiently express sets of genes whose products are needed at the same time.
5. Anatomy of an Operon
  1. Operons aren't just made up of the coding sequences of genes. Instead they also contain regulatory DNA sequences that control transcription of the operon. Typically, these sequences are binding sites for regulatory [roteins, which control how much the operon ins transcribed.
    1. The promoter, or the site where RNA polymerase binds, is one example of a regulatory DNA sequence.
  2. Most operons have other regulatory DNA sequences in addition to the promoter. These sequences are binding sites for regulatory proteins that turn expression of the operon "up" or "down".
    1. Some regulatory proteins are called repressors that bind to pieces of DNA called operators. When bound to its operator, a repressor reduces transcription (e.g by blocking RNA polymerase from moving forward on the DNA)
    2. Some regulatory proteins are activators. When an activtor is bound to a DNA binding site, it increases transcription of the operon (e.g by helping RNA polymerase bind to the promoter).
    3. Regulatory proteins are produced within an organism, they are encoded by genes in the bacteruim's genome. The genes that encode regulatory proteins are sometimes called regulatory genes.
    4. Many regulatory proteins can themselves be turned "on" or "off" by specific small molecules. The small molecule binds tot he protein, changing its shape and altering its ability to bind to DNA. For instance, an activator may only become active (able to bind to DNA) when it's attachedto a certain small molecule.
6. Operons may be inducible or repressible.
  1. Some operons are usually "off", but can be turned "on" by a small molecule. The molecule is called an inducer, and the operon is said to be inducible.
    1. For example, the lac operon is an inducible operon that encodes enzymes for metabolism of lactose. It only tirns on when the sugar is present. The inducer in this case is allolactose, a modified form of lactose.
  2. Some operons are usually "on", but can be turned "off" by a small molecule. The molecule is called a coressor, and the operon is said to be repressible.
    1. For example the trp operon is a repressible operon that encodes enzymes for synthesis of the amino acid tryptophan. This operon is expressed by default, but can be repressed when high levels of thr amino acid tryptophan is present. The corepressor in this case is tryptophan
Gene Regulation differences between Species
1. Differences in gene regulation makes the different cell types in a multicellular organism unique in structure and function.
  1. Gene regulation can also help us explain some of the with differences in form and function between different species relatively similar gene sequences.
2. Human and chimpanzees have genomes that are about 98% identical at the DNA level. Thee protein-coding sequences are different between human and chimpanzees, contributing to the differences between the species.
  1. 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 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.

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Eukaryotic Gene Regulation

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	Created by Erin Ancliffe about 7 years ago