gene expression and epigenetic regulation jessica laine and elizabeth martin

Gene Expression and Epigenetic Regulation

JESSICA LAINE AND ELIZABETH MARTIN

The Central Dogma of Biology

How does the cell control these processes?

Research Questions in the Fry Lab

What is the relationship between prenatal arsenic exposure and changes to gene expression?

Are any of the genes that are altered in association with arsenic controlled by the epigenetic mechanism DNA methylation?

How were these questions investigated?

38 newborns Arsenic

exposure DNA

Methylation Profiles

RNA (Gene expression) Profiles

Is there is a relationship between prenatal exposure to arsenic and functional epigenetic changes to newborn DNA ?

Microarray analysis was used to determine which genes exhibited differential expression

The microarray works by first extracting DNA or RNA and hybridizing different pieces representing different genes to a transcript

It allows us to measure how many copies of each gene is expressed (i.e. has transcript)

This can tell us whether there is no, some or a lot of RNA transcript in the cell

What is a heatmap and how do you read it?

Lower iAs Higher iAs

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334 U

-tA

s-a

ssocia

ted

tr

an

scri

pts

• N=38 subjects with range of arsenic exposure, cord blood (vein) isolated

• Multi-variable models for association between arsenic exposure-prenatal and gene expression

N=224

N=110

A heatmap is a way to visualize data trends

U-t

As

(µ

g/L

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Conclusions

There are 334 genes that show a change in transcript profiles in association with arsenic exposure in the 38 babies in the BEAR cohort

There are gene that expression changes in both a positive and negative way: some genes expression profiles increase with increasing arsenic exposure and some gene expression profiles decrease with decreased arsenic exposure

These changes suggest that prenatal arsenic exposure does affect a baby’sgene expression profile

Are any of the genes that are altered in association with arsenic controlled by the epigenetic mechanism DNA methylation?

The traditional view of DNA methylation

What would you expect to find?

What did we see when looking at individual genes?

What did we see when looking at individual genes?

DNA MethylationGene Methylation

RNA TranscriptGene Expression

Where do these measurements come from?

What conclusions can we draw from this?

Methylation does indeed control for some genes’ gene expression, in this study we found 16 genes were controlled by gene expression

Some of these genes were related to important birth outcome including gestational age and head circumference

Questions?

What did the researchers actually find?

This pattern is present across the entire genome!