LECTURE 7 (epigenetics and disease)

Question 1

Histone modification, where does it occur?

Answer 1

it occurs in histone tails which serve as a template for epigenetic modification. the modification carried here is reversible and covalent-

Question 2

which is the modification that occurs at the histone tails?

Answer 2

covalent and reversible. It’s a post-translational modification

Question 3

What does the histone code state?

Answer 3

“transcription of genes is highly modified by chemical alterations of histone proteins specially at the end”

Question 4

Cite some types of modifications.

Answer 4

methylation, acetylation, ubiquitination…

Question 5

Which type of modification in histone tails can happen more than once in the same a.a

Answer 5

methylation.

Question 6

How many combinations of modifications are there?

Answer 6

280 billions that cause thousands of effects

Question 7

do you always get transcription after histone modification?

Answer 7

no, it depends on the modification.

Question 8

What are the modifying enzymes that carry histone modification?

Answer 8

they are part of the chromatin remodeling complex

Question 9

What do modifying enzymes do to histones?

Answer 9

change the binding capability
shift nt position
cause repression of transcription
DNA repair..

Question 10

Two characteristics of modifying enzymes.

Answer 10

redundancy (can modify a single position several times by different enzymes)
specificity (can only target one position)

Question 11

do the modifying enzymes act intrinsically or extrinsically?

Answer 11

both, intrinsically on single nucleosome or extrinsically, many nucleosomes at a time

Question 12

Name and describe a couple of epigenetic diseases.

Answer 12

Rett syndrome is due to mutations in epigenetic effector proteins; intelectual disabilities, small hands, deregulation of imprinted genes, no verbal skills, can’t walk.

Fragile X syndrome: brain disability, no visual contact, hyperactivity big ears and testis: due to methylation in promoter seq leading to gene silencing.

Question 13

can cancer be caused by methylation?

Answer 13

yes, the histone modification and methylation causes epidermal papilomas

Question 14

What are genetic modifications?

Answer 14

alteration of DNA seq; chr rearrangements,mutation of genes, loss of genes…

Question 15

What are epigenetic modifications?

Answer 15

no change in DNA sequences; methylation, histone modification…

Question 16

Difference bt genetic and epigenetic modifications? do they act independently?

Answer 16

genetic involve change in DNA seq whereas epigenetic don’t and they can work in combination

Question 17

What’s the two-hit hypothesis?

Answer 17

the 1st hit is epigenetic e.g promoter methylation eliminating a 2nd copy of a gene the second hit is epigenetic or genetic result: carcinogenesis. It states that cancer is the result of an accumulation of mutations

Question 18

Which mechanisms involved in DNA methylation can cause cancer?

Answer 18

• accumulation of CpG islands 5mC is more mutagenic than C

- allelic imprinting: deregulation of imprinting might lead to cancer

Question 19

give an example of allelic imprinting that leads to cancer?

Answer 19

the igf2 gene is activated in normal paternal cells and off in maternal ones. if it’s on in maternal ones – > leads to cancer.

Question 20

What factors affect DNA methylation levels?

Answer 20

• age: because CpG islands become hypermethylated
• nutrition: nutrition supplies methyl groups a diet in folate and methionine alters DNA methylation.
• environment: arsenic and cadmiun compounds alter methylation of certain DNA regions associated with cancer

Question 21

Role of acetylation in cancer?

Answer 21

it has to do with the cell cycle regulation and over expression of acetylating enzymes can cause cancer because it represses a tumor suppressor gene:
cancers that can be caused by acetylation: colon, epithelial, breast…

Question 22

what are chromatin remodeling complexes? role in cancer?

Answer 22

they’re multisubionit complexes containing ATPase that are involved in cancer and can cause covalent modifications in histones

Question 23

Epigenetic processes that are deregulated in cancer: (5)

Answer 23

DNA methylation itself is mutagenic
Deregulated genomic DNA methylation patterns
Deregulated genomic imprinting
Mutation of chromatin modifying enzymes
Mutation of chromatin remodeling complexes

Question 24

Role of histones:

Answer 24

• can act intrinsically or extrinsically
• are modified by modifying enzymes
• can recruit other proteins
• they’re modified covalently and reversible
• Participate in the regulation of many processes Transcription, DNA repair, chromatin assembly, silencing, heterochromatin formation