2/16/2018

Control of Gene Expression

in Eukaryotes

X-inactivation
Histone modification
Chromatin remodeling
DNA methylation

Control of Gene Expression in Eukaryotes

Learning Goal: Understand mechanisms that help control gene expression in eukaryotes

After the pre-class assignments you should be able to:

• Describe the role of histone proteins in DNA packaging, nucleosome formation, and chromatin structure
• Discuss how histones are chemically modified to increase or decrease the expression of a gene
• Describe how DNA methylation affects gene expression in eukaryotes
• Discuss the role of Xist in regulating gene expression at the chromosome level and why this is important
for regulating gene dosage
• Describe how alternative splicing allows for multiple gene products to be produced from the same gene
• Describe the role of posttranslational protein modifications in the control of gene expression

By the time you take the final exam you should also be able to:
• Explain how chromatin packaging affects gene expression in eukaryotes
• Predict the effect of mutations in gene regulatory elements on gene expression
• Predict how DNA methylation patterns and histone acetylation will affect gene expression
• Evaluate the effect of different chromatin modifying enzymes on gene expression

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What does DNA actually look like?

Remember this?

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What is missing from this picture?

“Liberating the promoter”

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Acetylated Histones

HDAC: HAT:
Histone Histone
deacetylase acetyltransferase

Another View

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Acetylation is just a small

chemical modification
Acetylation
modification
Amino
acid R Acetylation
group in a by HATs
histone
protein Deacetylation
by HDACs

Multiple players in histone modification

SWI/SNF requires energy from the
hydrolysis of ATP in order to slide histones

DNMT

HAT – histone acetyl transferase

HDAC – histone de-acetylase
DNMT – DNA methyl transferase

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DNA methylation helps long-term

gene repression
DNMT = DNA
DNMT Cytosine is methylated
methyl transferase

Many repressors
don’t completely
block gene expression

DNA methylation
contributes to
completely shutting
off gene expression

Methylated cytosine has a small

chemical modification

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What can happen when expression

patterns are altered in a cell?
• “Dosage” effects
• Expressing genes at
the right time and
place
• Chromosomal
trisomy occurs when
someone ends up
Are all genes with three copies of
always expressed a chromosome
all the time? instead of two

Researchers have tried using Xist as a potential

gene therapy treatment for trisomy.
The researchers added an
X-chromosome inactivation
center (XIC) to one copy of
chromosome 21. They then
looked at APP mRNA and
Xist on three different days.

APP mRNA appears green

Xist appears red

APP is a gene located on chromosome 21

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Researchers have tried using Xist as a potential

gene therapy treatment for trisomy.

APP is a gene located on chromosome 21