MOL - Regulation [LESSON]

Regulation

How does the DNA in somatic (body) cells compare to each other?

Almost every somatic cell in the body has EXACTLY the same DNA!

If each cell has the same DNA, how is it that cells or organs are different? Why do cells in the eye differ so dramatically from cells in the liver? For example, you have proteins that detect light in your eyes. To make those proteins, the DNA code in your eye cells must hold the code…but how is the gene turned on in your eye cells and turned off in other parts of your body?

The genetic content of each somatic cell in an organism is the same, but not all genes are expressed in every cell.

The genetic content of each somatic cell in an organism is the same, but not all genes are expressed in every cell. The control of which genes are expressed dictates whether a cell is (a) an eye cell or (b) a liver cell. It is the differential gene expression patterns that arise in different cells that give rise to (c) a complete organism. This is important because your body saves a ton of energy by only expressing proteins when needed. Protein synthesis is extremely energetically expensive. Gene regulation also allows different responses by cells to different environments. For example, a bacterial cell can create different protein enzymes necessary to digest different food sources – this can mean the difference between life and death for a cell!

Prokaryotic versus Eukaryotic Genome

Let’s review some major differences between the prokaryotic and eukaryotic genomes.

  1. Eukaryotes have MORE DNA overall.
  2. Eukaryotes have LESS DNA that codes for proteins.
  3. Prokaryotes have one circular chromosome and eukaryotes have linear chromosomes in multiples of two.
  4. Prokaryotes have extra smaller loops of DNA called plasmids that are separate from the chromosomal DNA. Most eukaryotes do not.
  5. Transcription and translation often happen simultaneously in prokaryotes because they do not have a nucleus to separate the two processes.

Prokaryotic Regulation

In bacteria, related genes are often found in a cluster on the chromosome, where they are transcribed from one promoter (RNA polymerase binding site) as a single unit. Such a cluster of genes under control of a single promoter is known as an operon. Operons are common in bacteria, but they are rare in eukaryotes such as humans.

An operon with the promotor shown and three structural genes.

Regulation is a very complex subject and involves regulatory proteins that bind to regulatory DNA sequences to control transcription of the gene. A great analogy that we can make is with light switches. We can think of an on/off switch (repressor) and a dimmer switch (activator). 

A repressor protein acts like an on/off switch by binding to a regulator sequence called the operator. If the repressor protein is bound, RNA polymerase is physically blocked and the gene cannot be transcribed.

If the repressor protein is bound, RNA polymerase is physically blocked and the gene cannot be transcribed.

An activator protein acts like a dimmer switch because it can turn up the speed of transcription. The activator binds at or near the promoter to help RNA polymerase to bind (more polymerases can bind per unit of time). This increases the transcription rate.

Watch the video below to learn more about prokaryotic regulation using the two most famous examples – the lac operon and the trp operon  It is important to take detailed notes on this video.

Eukaryotic Regulation

Eukaryotes have much more DNA, but proportionally less that actually codes for proteins. This means that there’s a LOT of regulatory DNA in eukaryotes! Eukaryotes have a few interesting mechanisms to further regulate gene expression. First, let’s discuss the general differences between eukaryotic and prokaryotic regulatory mechanisms.

In some eukaryotic genes, there are regions that help increase or enhance transcription. These regions, called enhancers, are not necessarily close to the genes they enhance. They can be located upstream of a gene, within the coding region of the gene, downstream of a gene, or may be thousands of nucleotides away.

Enhancer regions are binding sequences, or sites, for transcription factors. When a DNA-bending protein binds to an enhancer, the shape of the DNA changes. This shape change allows the interaction between the activators bound to the enhancers and the transcription factors bound to the promoter region and the RNA polymerase to occur. Whereas DNA is generally depicted as a straight line in two dimensions, it is actually a three-dimensional object. Therefore, a nucleotide sequence thousands of nucleotides away can fold over and interact with a specific promoter. An enhancer is a DNA sequence that promotes transcription. Each enhancer is made up of short DNA sequences called distal control elements. Activators bound to the distal control elements interact with mediator proteins and transcription factors.

An enhancer is a DNA sequence that promotes transcription.

Eukaryotic repressors work very much in the same fashion, but they bind with regulatory sequences called silencers

Eukaryotic DNA is wrapped around histone proteins almost like a spool and thread. Histones help to control transcription rate because the DNA can coil tightly, blocking access to the promoter, or relax and allow transcription. Modifications such as acetylation or methylation of the histones can alter how tightly DNA is wrapped around them.

The methylation of DNA and histones causes nucleosomes to pack tightly together.

Nucleosomes can slide along DNA. When nucleosomes are spaced closely together (top), transcription factors cannot bind and gene expression is turned off. When the nucleosomes are spaced far apart (bottom), the DNA is exposed. Transcription factors can bind, allowing gene expression to occur. Modifications to the histones and DNA affect nucleosome spacing.

Watch the Eukaryotic Regulation video to learn more about eukaryotic regulation.

Try the Operon fill in the black activity below, and drag the word to the correct place, then click next.

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