Epigenetic Gene Regulation

Question 1

Epigenetic Control

Answer 1

Heritable changes in gene expression that do not involve changes in DNA nucleotide sequence itself

Question 2

Genomic Imprinting

Answer 2

• Nonequivalence in expression of alleles b/n paternal and maternal genomes at a certain gene loci
• Imprinting affects the expression of a gene but not primary sequence of DNA

Question 3

Imprinted Genes

Answer 3

• Differ from other autosomal loci in that only paternal or material allele is expresses in relevant tissue, whereas vast majority of unimprinted genes are expresses from both maternal and paternal alleles
  
  • Gene that is maternally imprinted = only expresses paternal allele
  • Gene that is paternally imprinted = only expresses maternal allele

Question 4

Uniparental Disomy

Answer 4

• inheritance of 2 copies of a full chromosome (or its portions) from 1 parent

Question 5

2 Mechanisms of Epigenetic Control

Answer 5

1- DNA methylation

2- histone modification

Question 6

What does DNA methylation cause?

Answer 6

Repression of gene expression

Question 7

Maintenance methylation

Answer 7

perpetuation of a preexisting methylation pattern (Carried out by Dnmt1)

When methylated DNA is replicated the new strand is not automatically methylated but needs to be REMETHYLATED by DNA methyltransferases (add methyl groups to cytosine using methylated strand as a template)

Question 8

De novo methylation

Answer 8

New methylation of completely demethylated DNA

Carried out by Dnmt1, Dnmt3a and Dnmt3b

Question 9

Epigenetic reprogramming during development and sec-specific DNA methylation

Answer 9

• After fertilization…male or female embryo will have 1 copy of paternal imprinted chromosome and maternal imprinted chromosome
• Then when that fertilized egg is a grown person and they undergo oogenesis or spermatogensis the imprints are erased by removing epgenetic markers and new imprints established in imprinted region
  
  • If male… new imprints are both paternal
  • If female…new imprints are both maternal
  • **So gametes carry mono allelic imprint while all other somatic cells in that person carry one chromosome of ea imprint type

Question 10

HATS

Answer 10

Specific histone acetylation transferases (HATs)

add acetyl groups to lysine in histone —> open transcriptionally active chromatin

Question 11

HDACs

Answer 11

histone de-acetylases

• Histone deacetylation —> repression of gene expression
• HDAC’s remove acetyl group from histones —> chromatin condensation and inhibition of gene expression

**HDAC inhibitors are a new class of anticancer agents

Question 12

histone methyltransferases

Answer 12

Methylate histones at some lysine residues –> transcriptional repression

Question 13

Histone code

Answer 13

histone modifications that can influence gene expression independent of DNA sequences

Question 14

Prader-Willi Syndrome (PWS) vs Angelman Syndrome (AS)

Answer 14

• About 70% PWS cases due to deletion in a region of PATERNAL chromosome and 30% cases due to uniparental disomy of chromosome 15 from MOTHER (so only have 2 copies from mother instead of one from ea parent)
• 70% AS due to deletion of a region in MATERNAL chromosome and 5% due to uniparental disomy of chromosome 15 from FATHER (rest of cases due to mutations in maternal gene, ICs and unknown cause)