1. DNA AND RNA
12-5 Gene Regulation

2. Target Learning Students will be able to: Describe a typical gene.
Describe how the lac genes are turned off and on.
Explain how most eukaryotic genes are controlled.
Relate gene regulation to development.

3. Gene Regulation
Only a fraction of the genes in a cell are expressed at any given time.
An expressed gene is a gene that is transcribed into RNA.
How does the cell determine which genes will be expressed and which will be silent?
Some DNA sequences serve as promoters, binding sites for RNA polymerase.
Other DNA sequences serve as start and stop signals for transcription.
Cells are filled with DNA-binding proteins that attach to specific DNA sequences and help to regulate gene expression.

4. Gene Regulation
Start codon: A group of three adjacent nucleotides, AUG in mRNA (ATG for DNA replication), that code for methionine and initiate polypeptide formation (the start of DNA replication or mRNA transcription).
Stop codons: Any of three mRNA sequences (UGA, UAG, UAA) that do not code for an amino acid and thus signal the end of protein synthesis (transcription).

5. Gene Regulation
A typical gene includes start and stop codons. There is a promoter to one side of the gene. “Regulatory sites” are places where other proteins bind directly to DNA sequences to regulate transcription and to help determine whether a gene is turned on or turned off.

6. Gene Regulation: An Example
operon: a group of genes that operate together.
In the bacterium Escherichia coli, a cluster of three genes are turned on or off together – these genes are called the lac operon because they must be expressed in order for E. coli to be able to use lactose (a sugar) as food.
Why must the lac genes be turned on in order for E. coli to use lactose for food?
Lactose is composed of two simple sugars, galactose and glucose.
To use lactose for food, lactose must cross the cell membrane and the bond between galactose and glucose broken – this is accomplished by proteins coded for by genes of the lac operon.

7. Gene Regulation: An Example
The lac genes are turned off by repressors and turned on by the presence of lactose.
On one side of the operon’s three genes are two regulatory regions: the promoter and the operator.
In the promoter (P), RNA polymerase binds and then begins transcription.
The other region is the operator (O), where a DNA-binding protein called the lac repressor binds and prevents transcription.
The binding of the repressor protein turns the operon “off” by preventing the transcription of its genes.

8. Gene Regulation: An Example
The lac repressor protein has a binding site for lactose.
When lactose binds to the repressor, it causes a change the repressor’s shape that makes it fall off the operator, thus allowing transcription to begin.
The lac operon shows one way in which prokaryotic genes are regulated.
Cells turn genes on and off as needed.

9. Eukaryotic Gene Regulation
Gene regulation in eukaryotes is similar but much more complex.
Operons are generally not present.
TATA box: short section of DNA (about 30 base pairs long of TATATA or TATAAA) that helps position RNA polymerase by marking a region just before the start codon.
Eukaryotic promoters, consisting of a series of short DNA sequences, are usually found just before the TATA box.
Enhancer sequences are located upstream of the start signal.
An enormous number of proteins can bind to different enhancer sequences.

10. Eukaryotic Gene Regulation
Enhancer proteins may open up tightly packed chromatin, attract RNA polymerase, block access to genes, as well as other functions.
Why is gene regulation in eukaryotes more complex?
Cellular specialization requires genetic specialization.
Each cell carries the complete genetic code, but only a fraction of the code needs to be expressed in each cell type.
Keratin, an important protein in skin cells, is not produced in blood or liver cells.

11. Development and Differentiation
When a cell is fertilized and begins dividing, the new cells not only grow and divide, but they also undergo differentiation, i.e., they become specialized in structure and function.
The hox genes, control the differentiation of cells and tissues in the embryo.
The hox genes are the genes identified as the “genetic toolbox” in the video clip we watched.
The function of the hox genes in all animals is essentially the same – to tell the cells of the body how they should differentiate as the body grows.

12. Development and Differentiation
The Pax 6 gene controls eye growth in Drosophila; a similar gene guides eye growth in mice and other mammals.
When a copy of the mouse gene is inserted into the “knee” region of a Drosophila embryo, the resulting fruit fly grew an eye on its knee.

13. Development and Differentiation
In fruit flies, a series of hox genes along a chromosome determines the basic structure of the fly’s body. Mice have very similar genes on four different chromosomes. The color bars show the approximate body area affected by genes of the corresponding colors.

14. Review What is the function of the promoter?
It’s the RNA polymerase binding site.
What codon sequence would you expect to find in the mRNA at the place where transcription starts?
AUG, the start codon.
At the place where transcription ends?
UAA, UAG, or UGA
What kinds of molecules bind to the regulatory sites of genes?
DNA-binding proteins
What is the action of DNA-binding proteins on genes?
They turn genes off or on.
In the lac operon, when is the repressor protein bound to the operator?
When lactose is not present.

15. Review
Why can’t transcription occur when the repressor is bound to the operator?
The repressor protein blocks RNA polymerase from binding to the promoter.
How does the presence of lactose help start transcription of the lac genes?
Lactose binds to the repressor protein, causing it to release from the operator site, and RNA polymerase can bind to the promoter.
How is the lac operon regulated?
It is turned off by repressors and turned on by the presence of lactose.
Describe how must eukaryotic genes are controlled.
Most are controlled individually and have regulatory sequences that are much more complex than those of prokaryotic genes.

16. Review What genes control cell differentiation during development?
The hox genes.
What is a promoter?
The region of mRNA where RNA polymerase binds and starts transcription.
How is the way hox genes are expressed in mice similar to the way they are expressed in fruit flies? How is it different?
The genes themselves are very similar and have the same function. In fruit flies, the genes are located on one chromosome. In mice, the genes are spread among four chromosomes.

17. Review
What is the scientific explanation of the striking similarity of genes that control development in animals?
Common patterns of genetic control exist because all these genes have descended from the genes of common ancestors.