Epigenetics (lecture 13)

Question 1

definition

Answer 1

Epigenetics is the study of inheritable alterations in
gene expression potential that are not caused by
changes in DNA sequence.

e.g. Somatic inheritance of epigenetic marks participates in
the maintenance of cell lineage characteristics

Question 2

imprinting

Answer 2

certain genes are expressed in a parent-of-origin-specific manner. (imprinted = silenced allele)

Question 3

Epigenetic processes lead to

Answer 3

Epigenetic processes lead to the condensation of
constitutively heterochromatic chromosome regions, i.e.
telomeres and centromeres.

Question 4

genetic defense

against viruses/transposons?

Answer 4

Transposons comprise about 45% of our genome
Exonic regions only about 2%!
or
When epigenetic silencing of transposon regions spreads into neighboring regions
this might lead to inadvertent silencing of these genes.

Question 5

Epigenetic processes are particularly relevant for

Answer 5

dosage
compensation. The Barr body (epigenetically silenced Xchromosome
in mammals) is a well-known example.

Question 6

barr body

Answer 6

epigenetically silenced Xchromosome
in mammals

female: xx
male: xy

in females one X is silenced -> barr body

(in flies not!)

Question 7

Epigenetic modifications are a means to adapt gene

regulatory programs to..

Answer 7

environmental cues – e.g.

nutrigenomics (metabolic stress)

Question 8

How Are Epigenetic Effects Realized?

Answer 8

Epigenetic processes determine the activity-status of
genes by regulating genomic condensation

(condesation = inactivation = heterochromatin)

Question 9

2 main components of epi code

Answer 9

dna methylation at CpG repeats: represses activity

recruits machinery: HDAC (histone deacetylase), nucleosome remodelling

histone modification:

Question 10

CpGs in houskeeping

Answer 10

CpG in CpG islands are mostly not methylated and
are in promotors of housekeeping genes!

(not methylated because they are housekeeping, always active chromatin)

Question 11

Once started, histone methylation

Answer 11

can spread over wide
genomic regions

autocatalytic expansion of
heterochromatic region.

block: Insulators block further expansion of heterochromatic
genomic regions:

insulators acetylate!

Question 12

HOW DO EPIGENETIC MODIFIERS IDENTIFY

THEIR CORRECT TARGET GENES?

Answer 12

Epigenetically regulated genes are often clustered

particularly imprinted genes – imprinting control regions

Question 13

Specialized RNAs can bind to specific genomic sequences

and target DNA remodeling complexes (at least in yeast)

Answer 13

RITS =
RNA-induced initiation of
transcriptional silencing

Question 14

HOW IS EPIGENETIC INFORMATION

INHERITED?

Answer 14

DNA methylation occurs via DNA methyl transferases:
maintenance versus de novo methylation

methylation is supplemented at the new synthesized strand during replication

Question 15

maintainance of condensation?

Answer 15

Condensated DNA regions can be wrapped in a coat of
proteins or RNAs

– example polycomb protein complex

• example X-chromosome silenced by Xist RNA

Question 16

Heterochromatization (85%) of Barr-bodies is mediated

through:

Answer 16

DNA-methylation
Strongly reduced histone acetylation
Methylation in H3-K9 and proteins
of the Polycomb-group

Question 17

principal mechanism to

guarantee somatic inheritance of epigenetic stamps

Answer 17

Maintenance methylation

Question 18

mosaic-like phenotypes

Answer 18

Random inactivation of X-chromosomes in early
embryogenesis and subsequent mitotic inheritance of
inactivation

Question 19

IS EPIGENETIC INFORMATION ALSO

TRANSGENERATIONALLY INHERITED

Answer 19

TRANSGENERATIONAL INHERITANCE OF
EPIGENETIC MARKS IS PRESENT FOR
IMPRINTED GENES (FEW HUNDRED).

Imprinting is passing on gender-specific epigenetic
information from the parents to the offspring

Example: Gender-dependent differential imprinting
of genes encoding Igf-2 and Igf2r.

Question 20

Methylation patterns during

gamete formation and embryogenesis

Answer 20

Methylation patterns are erased and reformed

imprinting is NOT a maternal inhertied phenomenon!

Question 21

example for imprinting

Answer 21

NUTRIGENOMICS – HOW FOOD AFFECTS

OUR (EPI)GENETIC DISPOSITION

Question 22

METASTABLE EPIALLELES

Answer 22

ALLELES WITH LABILE EPIGENETIC STATE
ARE CALLED

ALL METASTABLE EPIALLELES
CHARACTERIZED SO FAR ARE
ASSOCIATED WITH TRANSPOSON
INSERTION

Question 23

HOW CAN DIFFERENTIAL FEEDING OF
ADULTS AFFECT THE EPIGENETIC
CONSTITUTION OF OFFSPRING

Answer 23

1. FEEDING AFFECTS FETUS IN UTERO

2. FEEDING AFFECTS EPIGENETIC MARKS IN GAMETES

Question 24

metabolic syndrome

epidemy

Answer 24

Increased risk of: Diabetes mellitus type 2, atherosclerosis and cardiovascular
disease.

WHO estimate:
300 million people affected worldwide by 2025.

life-style causes to develop metabolic syndrome

Question 25

experimential evidence for transgenerational epigenetic influence

Answer 25

``` Dutch famine (1944): children and grandchildren of women having been pregnant during the winter of 1944 were smaller than on average ```

Question 26

transgenerational epigenetic influence caused by conditioning

Answer 26

olfactory experience and foot shocks F1 animals fathered by conditioned males are more sensitive to corresponding cues F2 animals grandfathered by conditioned males have larger receptive brain regions for conditioning odorant

Question 27

multistep process

Answer 27

differentiate between: somatic epigenetic changes somatic epigenetic changes transferred to the germ line -> subsequent generations return to the baseline in the absence of recurrent stress recurrent stress leads to new somatic changes transferred to the germline