Control of Gene Expression

Chapter 16

Contolling Gene Expression

What does that mean? Regulating which genes are being

expressed transcribed/translated i.e. made into proteins

Not all genes are expressed all of the time

Controlling Gene ExpressionWhy do cells control gene expression? Each cell in an organism contains the

exact same set of DNA (i.e. 6 billion bp, ~30,000 genes)

What is the difference, then, between a skin cell and a nerve cell? The proteins found within the cell, i.e. the

genes that are expressedAllows for the process of differentiation

Controlling Gene Expression

All organisms regulate when and for how long a gene is on

This regulation allows for the conservation of energy

In eukaryotes differential gene expression is what creates the different cell types

Too much or too little expression can lead to disease, aging, etc.

Control of Genes

Regulatory proteins interact with DNA, RNA or other proteins to control the expression of genes

Transcription factors are regulatory proteins which interact with DNA at specific sequences to regulate gene activity

Two types of control: Negative control slows down or stops gene

activity Positive control promotes gene activities

Gene Control in Prokaryotes

No nucleus separates DNA from ribosomes in cytoplasm

Translation occurs even before mRNA transcripts are finished

Control functionally related genes together by grouping them into units called OperonsE.g. enzymes in a biosynthesis pathway

Operons in Prokaryotes Consist of a Regulatory Gene, Operator,

Promoter and the Structural genes they control

Transcription of these genes is initiated by one promoter, and controlled by a single operator

Transcribes as 1 unit, and a single mRNA is made, which is later translated into one polypeptide, which is later cleaves into individual proteins - polycistronic

Polycistronic Expression

Inducible Operon - Lac Operon Encodes genes necessary to process lactose Not needed unless lactose is present If there is no lactose:

Lac Operon

RNA Polymerase

Repressor

Regulatory gene

Structural genes not transcribed

Operator

Inducible Operon - Lac Operon

What happens when lactose is present? Need to make lactose-digesting enzymes Lactose binds allosterically to regulatory protein:

Inducible vs. Repressible Operons

Inducible operon (e.g. Lac operon) usually functions in catabolic pathways, digesting

nutrients to simpler molecules produce enzymes only when nutrient is available cell avoids making proteins that have nothing to do

Repressible operon (e.g. Tryp operon) usually functions in anabolic pathways

synthesizing end products when end product is present cell allocates

resources to other uses

Eukaryotic Gene Expression

MUCH more complicated that prokaryotic control

Most genes in eukaryotic cells are turned off at any given point Only 5-10% of genes are being expressed at any

point

Controlling gene expression occurs at several different points in the process:

Mechanisms of Gene Control in Eukaryotes

Chromatin Structure

Eukaryotic DNA wraps around histones, is further structured into nucleosomes• Promoters inaccessible

Chromatin remodeling makes gene promoters more accessible• Activators recruit remodeling complexes that

displace nucleosomes• Activators recruit enzyme that acetylates and

loosens histone assocation with DNA

Chromatin Remodeling

Eukaryotic gene organization

DNA

Regulatorysequences

Enhancer

TATAbox

Promoter

5' UTR

Transcription unit of gene

Exon Exon ExonIntron Intron

3' UTR

Transcription in Eukaryotes

Transcription factors bind to the TATA sequence within the promoter of gene to be transcribed

RNA polymerase binds to the transcription factors (initiates low levels of transcription)

Activators bind to enhancer sequences (may be located far from the gene)

Activators bind to RNA polymerase and trigger it to begin transcription (high level of transcription)

Transcription in Eukaryotes

Transcriptionbegins

Initial generaltranscription factor

Additional generaltranscription factors

Transcription complex

TATA box

Promoter

RNA polymerase

Site wheretranscription starts

DNA

DNA

The first generaltranscription factor recognizes and binds to the TATA box of a protein-codinggene’s promoter.

1

2 Additional general transcription factors and then RNA polymerase add to the complex, and then transcription begins.

Controlling transcription in Eukaryotes

Transcription regulation in Eukaryotes

DNA sequences Promoters Enhancers Other regulatory

sequences

Proteins Transcription

factors Activators Inhibitors

Eukaryotic Gene Expression

Regulates cell cycle Controls development (Homeo box genes) Controls differentiation

….and lots, lots more!

Apoptosis

Programmed cell death

Signals unleash molecular weapons of

self-destruction

Cancer cells do not commit suicide on cue