epigenetics

Question 1

Epigenetics

Answer 1

Epigenetics: inheritance from cell to cell or organism-to-organism by changes in chromatin and/or DNA, but not the DNA sequence itself.

Allows for extensive cell-type specificity and changes in normal cell physiology

Question 2

THe DNA sequence is the same in all cells except __ and __ genes.

Answer 2

Ig and TCR genes

Question 3

DNA & chromatin epigenetics change with aging, environment, by individual, and by disease.

What are the 3 main forms of epigenetics?

Answer 3

1. Methylation or Hydroxymethylation of C
   
   1. ​Usually methylation
   2. CpG dyad
   3. In vertebrates and higher plants
2. Inherited changes in chromatin structure
   
   1. ​Methylation, acetylation, histone phosphorylation
   2. Alterations in histone content
   3. Changes involving which proteins are incorporated into chromatin
   4. In euks
3. Non-coding (nc) RNA that stably associates with chromatin

Question 4

CpG dyad

Answer 4

5’-CpG-3’

This is the predominant location of methylated or hydroxymethylated cytosines. The C’s to get methylated are on adjacent basepairs.

Question 5

The exact position of a chromatin modification is often critical.

Answer 5

Ex) Histone 3 (H3) methylation at Lysine4 promotes transcription initiation and opening of chromatin, but at Lysine 9 it inhibits transcription and closes teh chromatin

Question 6

Noncoding RNA (ncRNA) isn’t useless because

Answer 6

Many change chromatin modifications.

Ex) XIST RNA

Question 7

Histone modifications, some non-histone proteins, and many ncRNAs are transmitted from cell to progeny cell.

This helps to…

Answer 7

• Establish cell type-specific patterns of open or closed chromatin (thus, activating or repressing) around genes
• Creates many co-regulated gene clusters of open or closed chromatin

Question 8

What is the importance of 5hmC (hydroxymethylation) in DNA?

Answer 8

• Especially high amounts of 5hmC in DNA of Purkinje neurons - important fo rneural funciton
  
  • 5hmC is more unstable than 5mC –> flexibility
• Changes in DNA 5mC and 5hmC are critical to differentiation and many diseases
• Can be a stable base in DNA with its own funcitons
• Can help regulate transcription (in a different way from 5mC)
• Can also serve as a transient intermediate from 5mC to unmethylated cytosine.

Question 9

Most DNA methylation patterns are established when?

Answer 9

During embryogenesis

Question 10

TET enzymes

Answer 10

DEmethylate

Question 11

CpG pair

Answer 11

If the top strand is methylated, so is the bottom strand

If the bottom strand is methylated, so is the top strand

Question 12

Maintenance methylation

Answer 12

When a CpG pair is split apart for DNA synthesis, there’s a brief period where theres a methylated CpG on one strand and not the other –> maintenance methylation methylates the new CpG

This makes up most of the DNA methyltransferase activity in postnatal cells

Question 13

De novo methylation

Answer 13

Changing methylation patterns in the early embryo; methylate a previously unmethylated CpG pair

Question 14

Loss of much of DNA 5hmC perturbs hematopoiesis and leads to

Answer 14

myeloid neoplasms

Question 15

DNA methylation affects transcription

Answer 15

Can affect chromatin structure, pre-mRNA splicing, and recombination

Question 16

The most frequent place to find point mutations and SNPs is at

Answer 16

CpG’s because 5mCs are often deaminated to thymine

5mC residues are hot spots for mutation

Question 18

CpG islands

Answer 18

Typically u**nmethylated CpG-rich DNA sequences at the 5’ ends of genes (usually housekeeping genes).

Overlaps with 70% of promoters, both downstream and upstream - making the promoters much easier to find.

Question 19

A CpG island at a promoter. If it goes from mostlyunmethylated to mostly methylated, what does this do to gene expression?

Answer 19

METHYLATION REPRESSES

Question 20

Cancer & CPG Islands

Answer 20

In cancer, some promoters (such as those of tumor suppressor genes) get turned off by methylation

Question 21

Methylation & imprinting

Answer 21

Methylation regulates imprinting

Question 22

X-inactivation and methylation

Answer 22

Methylation is important for maintaining the silencing of XIST and X_inactive genes

Question 23

DNA methylation also silences foreign DNA and transposable elements.

Question 24

ICF

Answer 24

immunodeficiency birth defect; the heterochroamtin near the centorsome in chormsomes 1& 16 forms multi-armed chromosomes

–> the satellite DNA here is normally highly methylated, but now gets demethylated

Question 25

How do abnormal increases, abnormal increases, and no change in DNA methylation contribute to cancer?

Answer 25

• Abnormal increases- hypermethylate the CpG island promoter of a tumor suppressor gene
  
  • ​Inactivate 1 of the alleles by hypermethylation, and the other by deletion/mutation OR
  • Inactivate both by hypermethylation