GENE REGULATIONch 18CH18

Bicoid is a protein that is involved in determining the formation of the head and thorax of Drosophila.

I. Overview of gene regulation

• Both prokaryotes and eukaryotes regulate gene expression in response to environmental conditions

• They only make those proteins that they need to function, often only making those proteins at specific times

• This was favored by natural selection. Since all organisms do this, it evolved early

• In multicelled eukaryotes this also regulates development and is responsible for creating the different cell types

II. Gene regulation in Prokaryotes

A. General characteristics of prokaryotic gene regulation: the operon

• Operon: cluster of functionally related gees under the control of a single on/off switch: the operator

• An operon contains the promotor, the operator, and all the genes under their control

• The operator binds repressor proteins that stop transcription by preventing RNA polymerase from binding to the promoter

• Some operons are repressible operons: they are usually on and repressor turns them off (trp operon)

• Some operons are inducible operons: they are off and inducer turns them on (lac operon)

• Inducible operons are part of catabolic pathways while repressible operons are part of anabolic pathways

B. The lac operon (an inducible operon)

• Involved in the breakdown of lactose for energy when no glucose is around

• In order for the lac operon to be on: o Cap protein must bind

to activator site Glucose prevents CAP from binding

o Repressor must be off of the operator

http://highered.mcgraw-hill.com/sites/0072556781/student_view0/chapter12/animation_quiz_4.html

C. Trp operon (a repressible operon)

Involved in the production of tryptophan, an amino acidTrp operon is on UNLESS there is excess tryptophan

http://highered.mcgraw-hill.com/olcweb/cgi/pluginpop.cgi?it=swf::535::535::/sites/dl/free/0072437316/120080/bio26.swf::The+Tryptophan+Repressor

III. Eukaryotic gene regulation

• Multicelled eukaryotes are more complex than prokaryotes so gene regulation occurs at many levels

• Gene regulation is designed to: o Maintain homeostasis o promote cell specialization

thru differential gene expression

A. Regulation of Chromatin structure

• Heterochromatin is tightly packed thus genes can’t be transcribed– Acetylation of histones loosens the

heterochromatin allowing it to be transcribed– Methylation condenses the DNA preventing it

from being transcribed which may play role in gene inactivation during differentiation

Sometimes these chemical modifications of DNA can be passed on to offspring. This is called epigenetics

http://learn.genetics.utah.edu/content/epigenetics/

B. Transcriptional control in Eukaryotes

1. Structure of a typical eukaryotic gene

• Upstream control elements: regulate transcription initiation by binding transcription factors

• Promoter: starts transcription• Coding sequence: in between promoter and

termination sequence

2. role of transcription factors

• general transcription factors allow transcription to occur

• activators are transcription factors that bind to enhancers upstream and induce transcription

• repressors are transcription factors than bind to silencers upstream and inhibit transcription

• http://highered.mcgraw-hill.com/sites/0072437316/student_view0/chapter18/animations.html#

C. Post-transcriptional control

• Allows cell to fine tune gene expression quickly in response to environmental changes

1. Alternate gene splicing

Production of different mRNAs from the same primary transcript depending on which exons are spliced together

2. Rate of mRNA degradation

• There are sequences in 3’end of mRNA that regulate its lifespan

• The quicker the mRNA is degraded, the less protein made

3. Initiation of translation

• Regulatory molecules can bind to mRNA that block initiation of translation

4. Protein processing and degradation

• If a protein is degraded it can’t be used

5. RNA interference

• Parts of the genome don’t code for proteins but produce other types of RNA

• RNA interference is the inhibition of gene expression by these RNAs

• Small interfering RNAs (siRNA) bind to mRNA to induce its degradationhttps://www.youtube.com/watch?v=cK-OGB1_

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IV. Differential gene expression and development in multicelled eukaryotes

• Fertilized egg divides by mitosis to produce all cells in multicelled eukaryotes– Cell division produces identical cells– Cell differentiation produces specialized cells thru

differential gene expression– Morphogenesis results in shaping of organism

• All three events are based on processes that occur at the cellular level

• Since transcriptional activators stimulate transcription, then different cells must have different sets of transcriptional activators

Different cells express different sets of genes What “tells” a cell which genes to express?

A. Cytoplasmic Determinants and Induction1. Cytoplasmic Determinants

• proteins, mRNAs, and organelles aren’t distributed evenly in a fertilized egg cell

• many of these proteins and mRNAs are cytoplasmic determinants that influence the fate of the cells

• when cell divides, determinants are not equally distributed

• therefore, nuclei in each cell are exposed to different determinants. This helps direct what genes are expressed during cell differentiation

2. Induction• As the number of cells

increases, different embryonic cells secrete signal molecules that affect gene expression in neighboring cells thru the cell signaling pathway

• This results in changes in gene expression

• Induction and cytoplasmic determinants lead to formation of 3 germ cell layers and ultimately all of the specialized cells in organs and tissues

• Once induction occurs and certain cells start expressing different genes, those cells are determined to become a specific cell type

• The expression of these specific genes leads to expression of other genes resulting in cell differentiation

IV. Gene regulation and Cancer

A. Cell Cycle control• Control of cell cycle is like accelerator and

break• When new cells are needed, accelerator is

used• When new cells not needed brake is used

B. Proto-oncogenes

• Are normal proteins that stimulate progression thru the cell cycle

• Many are intracellular cell signaling molecules involved in activating transcription

• Mutations cause proto-oncogenes to become oncogenes

• Results in overstimulation of cell division

Ex: Ras proto-oncogene

– Normal ras is activated by binding of growth factor to its receptor

– This activated ras activates a series of protein kinases that activate a transcription factor which induces transcription of cell cycle stimulatory protein

– Mutated ras does not need growth factor activation

C. Tumor Suppressor genes

• Normal tumor suppressor genes inhibit cell division– Some repair DNA– Some involved in anchorage dependence– Some are part of cell signaling pathway that

inhibit cell division

Ex: p53• DNA damage activates p53 which induces

transcription of a protein that inhibits cell cycle• Mutation in p53 fails to induce transcription of

this protein