Epigenetics and Imprinting

Question 1

describe methylation via Dnmt3

Answer 1

• Dnmt3 methylates unmethylated DNA
• MeCP2 recruits either HDAC1 or Dnmt1
• HDAC1 deacetylates histones
• Dnmt1 methylates hemimethylated DNA

Question 2

describe DNA methylation of globin genes

Answer 2

• Occurs in embryonic human blood stem cells
• Switching of globin chains of hemoglobin occurs during fetal development in human
• This switching is regulated by changes in DNA methylation of control regions located in the promoter of the genes encoding the different forms of globin proteins

Question 3

describe ICF

Answer 3

• result of the mutation in the Dnmt3b gene

Question 4

describe Rett syndrome

Answer 4

• Results from a mutation in the X-linked gene methyl cytosine binding protein 2 (MeCP2)

Question 5

describe Beckwith-Wiedemann syndrome (BWS)

Answer 5

• children of IVF have a 4-9 fold higher chance of BWS
• maternal chromosomal arrangements of 11p15 (imprinted region)
• paternal uniparental disomy
• IVF causes abnormal DNA methylation of region 11p15

Question 6

describe RFLP digestion of methylated DNA

Answer 6

• If the DNA is methylated = large DNA fragments (travel less)
• if the DNA is not methylated = small DNA frag (travel more)

Question 7

describe methylation and cancer

Answer 7

• various tumor suppressor genes are abnormally methylated in some tumors
• genes such as IGF2 has been shown to be abnormally methylated and therefore shows abnormal gene expression levels
• treatment drugs include those that interfere with DNA methylation (decitabine) and histone deacetylation (sodium butyrate)

Question 8

describe post-natal care and the glucocorticoid receptor

Answer 8

• reduced methylation results in higher levels of glucocorticoid receptor and an ability to handle stress better
• methylation patterns of this gene are established during the first week of life and maintained in the adult

Question 9

describe age and epigenetic markers

Answer 9

• as we get older, the epigenetic markers on our genomes change in response to our different environments

Question 10

explain the influence of environmental exposure to children

Answer 10

• environmental exposure during pregnancy influences the mother, fetus and the offspring of fetus

Question 11

describe incontinentia pigmenti

Answer 11

• caused by a mutation of the X-linked IKBKG gene
• mutation is lethal in males and is only survived in females that have skewed X-inactivation in favor of the normal IKBKG allele