Heredity, Gene Regulation, and Development

I. Mendel's ContributionsII. Meiosis and the Chromosomal TheoryIII. Allelic, Genic, and Environmental InteractionsIV. Sex Determination and Sex LinkageV. LinkageVI. MutationVII. Gene Regulation

Heredity, Gene Regulation, and Development

I. Mendel's ContributionsII. Meiosis and the Chromosomal TheoryIII. Allelic, Genic, and Environmental InteractionsIV. Sex Determination and Sex LinkageV. LinkageVI. MutationVII. Gene RegulationA. Overview

All cells in an organism contain the same genetic information; the key to tissue specialization is gene regulation – reading some genes in some cells and other genes in other cells.

VII. Gene RegulationA. Overview

All cells in an organism contain the same genetic information; the key to tissue specialization is gene regulation – reading some genes in some cells and other genes in other cells.

B. Terminology

Inducers turn a gene on…Repressors turn a gene off…

An “operon” is a region of genes that are regulated as a unit – it typically encodes > 1 protein involved in a particular metabolic pathway.

VII. Gene RegulationC. The lac Operon in E. coli

VII. Gene RegulationC. The lac Operon in E. coli

When lactose is present, E. coli produce three enzymes involved in lactose metabolism. Lactose is broken into glucose and galactose, and galactose is modified into glucose, too. Glucose is then metabolized in aerobic respiration pathways to harvest energy (ATP). When lactose is absent, E. coli does not make these enzymes and saves energy and amino acids.

How do these little bacteria KNOW? : )

Lac Y - permease – increases absorption of lactose

Lac Z – B-galactosidase – cleaves lactose into glucose and galactose

Lac A – transacetylase – may code for enzymes that detoxify waste products of lactose metabolism.

VII. Gene RegulationC. The lac Operon in E. coli

VII. Gene RegulationC. The lac Operon in E. coli

1960 – Jacob and Monod proposed that this was an inducible system under negative control. (Because the presence of the substrate INDUCES transcription by SHUTTING OFF regulation).

Repressor RNA Poly

Repressor Gene

Operator

VII. Gene RegulationC. The lac Operon in E. coli

1960 – Jacob and Monod proposed that this was an inducible system under negative control. (Because the presence of the substrate INDUCES transcription by SHUTTING OFF regulation).

LACTOSE

VII. Gene RegulationC. The lac Operon in E. coli

1960 – Jacob and Monod proposed that this was an inducible system under negative control. (Because the presence of the substrate INDUCES transcription by SHUTTING OFF regulation).

LACTOSE

The binding of lactose changes the shape of the repressor (allosteric reaction) and it can’t bind to the operator.

VII. Gene RegulationC. The lac Operon in E. coli

Mutant analyses confirmed these results:

VII. Gene RegulationC. The lac Operon in E. coli

Mutant analyses confirmed these results:

VII. Gene RegulationC. The lac Operon in E. coli

Mutant analyses confirmed these results:

VII. Gene RegulationC. The lac Operon in E. coli

But it is even more complicated… if glucose AND lactose are present, the operon is OFF. This is adaptive, because it’s glucose the cell needs. If glucose is present, there is no benefit to break lactose down to get it. BUT HOW?

VII. Gene RegulationC. The lac Operon in E. coli

Within the promoter, there is a binding site for a Catabolic Activating Protein – basically a “transcription factor”. CAP needs to bind in order for the RNA Polymerase to bind. Cyclic-AMP activates CAP, causing an allosteric reaction so it can bind the promoter.

, lactose present

VII. Gene RegulationC. The lac Operon in E. coli

Within the promoter, there is a binding site for a Catabolic Activating Protein – basically a “transcription factor”. CAP needs to bind in order for the RNA Polymerase to bind. Cyclic-AMP activates CAP, causing an allosteric reaction so it can bind the promoter. So, the binding of CAP stimulates transcription, exerting positive control.

, lactose present

VII. Gene RegulationC. The lac Operon in E. coli

When Glucose is present, the concentration of c-AMP declines, it does not bind to CAP, and CAP does not bind to the Promoter; so the RNA Poly does not bind and the genes are off.

, lactose present

VII. Gene RegulationC. The lac Operon in E. coli

When Glucose is present, the concentration of c-AMP declines, it does not bind to CAP, and CAP does not bind to the Promoter; so the RNA Poly does not bind and the genes are off.

So, the lac operon is regulated first by the presence/absence of glucose; the needed nutrient… and then by the presence of lactose, which could be metabolized to produce glucose if necessary.

VII. Gene RegulationC. The lac Operon in E. coliD. Summary

These are the transcription factors that bind to enhancer and silencer regions of the human metallothionien IIA gene promoter region!!

- What does having all these modifiers allow for?

VII. Gene RegulationC. The lac Operon in E. coliD. Summary

- Many proteins can be made from the same gene, by splicing the m-RNA differently. Humans have 20-30K genes, but several 100,000 proteins!

A calcium regulator in the thyroid

A hormone made in the brain

VII. Gene RegulationC. The lac Operon in E. coliD. Summary

- miRNA (microRNA): quite similar, but as ss-RNA they bind m-RNA and just stop translation. They are involved in developmental regulation .

VII. Gene RegulationC. The lac Operon in E. coliD. Summary

- Post-translational processing

zygote

mitosis