Lecture 12

What major application of epigenetics begins Lecture 12?

Cellular differentiation and development.

What are stem cells?

Cells from which other cells with specialized functions can be generated.

What is pluripotency?

The ability of a cell to develop into cells representing the three primary germ cell layers.

What are induced pluripotent stem cells (iPSCs)?

Cells that have been reprogrammed back to an embryonic-like pluripotent state.

Why are iPSCs potentially useful?

They can provide an extensive source of different types of human cells.

What is X inactivation?

An epigenetic process involving silencing of an X chromosome.

What is genomic imprinting?

Monoallelic gene expression that occurs according to the parent of origin.

What does monoallelic expression mean?

Only one of the two alleles of a gene is expressed.

What determines expression of an imprinted gene?

Whether the allele was inherited from the mother or the father.

How do most genes differ from imprinted genes?

Most genes can be expressed from both maternal and paternal alleles, while imprinted genes show parent-of-origin-specific expression.

Approximately how many genes are controlled through genomic imprinting according to lecture?

About 150 genes.

What are maternally and paternally imprinted genes?

Genes whose expression depends on whether the allele came from the maternal or paternal parent.

Where are genomic imprints assumed to be established?

In germ-line cells.

What gene pair is used as the major imprinting example in lecture?

IGF2 and H19.

How are many imprinted genes arranged in the genome?

They occur in clusters.

Approximately what percentage of imprinted genes are found in clusters according to lecture?

About 80%.

What is an imprinting control region (ICR)?

A regulatory region that can control silencing across a cluster of imprinted genes.

What does DMR stand for?

Differentially Methylated Region.

What is a DMR?

A DNA region that differs in methylation depending on its parental origin or regulatory state.

What epigenetic mechanism is commonly used in genomic imprinting?

DNA methylation.

Besides DNA methylation, what other modification can participate in imprinting?

Histone modifications.

What does IGF2 encode/do?

IGF2 is an important fetal growth factor and acts as a mitogen for many cell types.

What is H19?

A long noncoding RNA involved in development and associated with tumorigenesis.

From which parental allele is IGF2 normally expressed?

The paternal allele.

From which parental allele is H19 normally expressed?

The maternal allele.

What is the normal expression pattern of the IGF2/H19 locus?

IGF2 is normally paternally expressed, while H19 is maternally expressed.

What is unusual about methylation at the IGF2/H19 region?

Differential methylation determines which parental allele is expressed.

What kinds of genes are many imprinted genes?

Growth factors or growth-regulating genes.

Why do many imprinting disorders originate during fetal development?

Many imprinted genes regulate fetal growth and development.

What three imprinting disorders are emphasized in lecture?

Prader-Willi syndrome, Angelman syndrome, and Beckwith-Wiedemann syndrome.

What type of disorder is Beckwith-Wiedemann syndrome?

A disorder of genomic imprinting.

What can cause Beckwith-Wiedemann syndrome according to lecture?

Abnormal patterns of DNA methylation that alter gene-expression patterns.

What general DNA methylation pattern has been observed in cancers according to lecture?

Hypomethylation.

What does hypomethylation mean?

A reduction in DNA methylation.

According to lecture, hypomethylation is a property of what cancers?

All cancers examined to date in the lecture material.

What environmental example is given for a strong link between environment and complex disease?

Smoking and lung cancer.

Can environmental factors induce epigenetic changes?

Yes. Environmental conditions can modify the epigenome and influence phenotype.

What dietary experiment was performed on pregnant mice in the lecture example?

Their diets were supplemented with methylation precursors including folic acid, vitamin B12, and choline.

What happened to coat-color variation after pregnant mice received methylation precursors?

Variation was reduced and shifted toward the pseudoagouti phenotype.

What did the mouse diet experiment demonstrate?

Maternal environmental conditions can influence offspring phenotype through epigenetic changes.

Can early-life experiences produce epigenetic changes?

Yes. Stress and maternal nurturing early in life can influence epigenetic regulation and later behavior.

What happened to newborn rats receiving low levels of maternal nurturing?

They had low glucocorticoid receptor (GR) expression and adapted poorly to stress as adults.

What happened to newborn rats receiving high levels of maternal nurturing?

GR expression increased and they adapted better to stress as adults.

What does the maternal-nurturing rat example demonstrate?

Early environmental experiences can induce epigenetic changes that influence gene expression and adult phenotype.

What is the major takeaway from Lecture 12?

Epigenetic regulation connects development, parental origin, and environmental exposures to stable differences in gene expression and phenotype.