Epigenetic Regulation in Health and Disease

Question 1

Heritable changes in gene function that occurs without a change in the DNA sequence

Answer 1

Epigenetics

Question 2

What are some common modifications to the genome?

Answer 2

DNA methylation, Histone Modification, Non-coding RNA

Question 3

All of the epigenetic phenomena are characterized by chemical modifications to

Answer 3

DNA itself (DNA Methylation), or to Histones (The proteins around which DNA is wound)

Question 4

In humans, DNA methylation typically occurs at the

Answer 4

Cytosine bases of DNA within CpG dinucleotides

Question 5

Associated with the 5’-end regulatory regions of almost all housekeeping genes, as well as with half of the tissue specific genes

Answer 5

CpG rich regions (“CpG Islands”)

Question 6

When these promoter CpG Islands are methylated, the associated genes tend to be

Answer 6

Transcriptionally inactive

Question 7

The correct expression of many tissue-specific, germline-specific, imprinted, and X-chromosome inactivated (in females) genes, as well as that of repetitive genomic sequences, relies largely on

Answer 7

DNA Methylation

Question 8

Play key roles in the erasure, establishment, and maintenance of DNA methylation patterns through development

Answer 8

Epigenetic modifications

Question 9

The extent of DNA methylation changes in an orchestrated way during mammalian development, starting with a

Answer 9

Wave of demethylation during cleavage

Question 10

However, after implantation, there is

Answer 10

Genome-wide methlyation

Question 11

An active process that strips the male genome of methylation within hours of fertilization

Answer 11

Demethylation

Question 12

In contrast, the maternal genome is passively demethylated during subsequent

Answer 12

Cleavage divisions

Question 13

The extent of methylation in the genome of gastrulating embryo is high, owing to de novo methylation, but it tends to decrease in specific tissues during

Answer 13

Differentiation

Question 14

Occurs rarely after gastrulation, but this phenomenon is seen frequently in cancer

Answer 14

De novo Methylation

Question 15

Which enzyme removes methyl groups?

Answer 15

Demethylase (dMTase)

Question 16

Which enzyme adds methyl groups

Answer 16

DNA methyl transferase (DNMT)

Question 17

Replication of somatic cells results in hemimethylated DNA, which is then fully methylated by

Answer 17

DNMT

Question 18

Negatively regulates transcriptional output

Answer 18

Transcription factor binding to methylated DNA sequence motifs

Question 19

DNA methylation is important in

Answer 19

1. ) Regulation of gene expression (i.e. tissue specific transcription)
2. ) Genomic imprinting

Question 20

An autism spectrum disorder with a monogenic origin

Answer 20

Rett Syndrome

Question 21

A progressive neurological disorder that is one of the most common causes of mental retardation in females

Answer 21

Rett syndrome

Question 22

What type of trait is Rett Syndrome?

Answer 22

X-linked dominant

Question 23

Children affected by Rett syndrome have a period of apparently normal development lasting

Answer 23

6-18 months

Question 24

What is the cause of most cases of Rett Syndrome

Answer 24

MECP2 gene mutations

Question 25

Capable of binding specifically to methylated DNA and represses transcription from methylated gene promoters

Answer 25

MECP2

Question 26

MECP2 is ubiquitously present, but is most abundantly expressed in the

Answer 26

Brain

Question 27

Los of function of MeCP2 in differentiated post-mitotic neurons likely results in the inappropriate overexpression of genes with potentially damaging effects during

Answer 27

Nervous system maturation

Question 28

The unequal expression of the maternal or paternal alleles of a gene

Answer 28

Genomic Imprinting

Question 29

The epigenetic tags on imprinted genes usually stay put for the life of the organism, but they are reset during

Answer 29

Egg and sperm formation (Thus why they are not passed to offspring)

Question 30

Imprinted genes play vital roles in

Answer 30

1. ) Embryonic growth 2. ) Neonatal behavior 3. ) Tissue or developmental stage-specific monoallelic expression patterns

Question 31

The SNRPN gene, producing small nuclear ribonucleoprotein N, being methylated during oogenesis but not spermatogenesis is an example of

Answer 31

Genomic imprinting

Question 32

An example of genomic imprinting because it is methylated during spermatogenesis but not oogenesis

Answer 32

The UBE3A gene

Question 33

Region that contains at least two imprinted genes, one maternally imprinted and one paternally imprinted

Answer 33

Chromosome 15

Question 34

If a child receives a chromosome 15 in which a large deletion removed the function of these genes from their father, and an (inactive) maternally imprinted gene from their mother, they will have

Answer 34

Prader-Willi Syndrome

Question 35

If a child receives the deleted chromosome 15 from their mother, and an (inactive) copy of the paternally imprinted gene from their father, they will have

Answer 35

Angelman syndrome

Question 36

Prader-Willi syndrome is indicated by

Answer 36

Mental retardation and Hyperphagia

Question 37

Angelman Syndrome is indicated by

Answer 37

Excessive laughter, seizures, and mental retardation

Question 38

In Prader-Willi syndrome, the maternal allele is imprinted by -No SNRPN protein is expressed from the imprinted maternal chromosome 15 SNRPN allele

Answer 38

Methylation

Question 39

In Angelman syndrome, the paternal allele is imprinted by methylation resulting in -Why a deletion in the mothers gene causes the syndrome

Answer 39

No expression of UBE3A protein by the UBE3A allele

Question 40

Histones can be reversibly modified in their amino-terminal tails, which protrude from the nucleosome core particle, by

Answer 40

1. ) acetylation of lysine 2. ) phosphorylation of serine 3. ) methylation of lysine and arginine residues 4. ) sumoylation

Question 41

The N termini of core histone proteins contain many lysine residues that impart a highly positive charge. These positively charged domains can bind tightly to the negatively charged DNA through

Answer 41

Electrostatic Interactions

Question 42

Tight binding between DNA and histones is associated with

Answer 42

Gene inactivity

Question 43

Neutralizes the positively charged histone tails, weakening their interaction with DNA (forming euchromatin) and allowing active transcription

Answer 43

Acetylation of Histone tails

Question 44

Which enzyme acetylates histone tails?

Answer 44

Histone acetyltransferase (HATs)

Question 45

A functional RNA molecule that is transcribed from DNA but is not translated into proteins

Answer 45

non-coding RNA -includes: miRNA, siRNA, piRNA, and IncRNA (long non-coding RNA)

Question 46

Long non-coding RNAs regulate epigenetics by

Answer 46

Chromatin remodeling, transcriptional regulation, post-transcriptional regulation, and as precursors for siRNAs

Question 47

What is an example of epigenetic regulation by long non-coding RNAs (ncRNAs)?

Answer 47

X-chromosome inactivation

Question 48

X-chromosome inactivation involves which two IncRNAs?

Answer 48

1. ) Xist (of X-inactive specific transcript) | 2. ) Tsix (its antisense transcript, a negative regulator of Xist)

Question 49

Transcribed from the X-inactivation center (XIC) of the inactive X chromosome (Xi)

Answer 49

The lncRNA Xist

Question 50

What does the Xist RNA do?

Answer 50

Covers the entire chromosome and silences gene expression through epigenetic modifications of histones and DNA (thus inactivating the X chromosome)

Question 51

Can bind to the X-inactive specific transcript (Xist) and inhibit its action, thus preventing X-inactivation -antisense to Xist RNA

Answer 51

Tsix

Question 52

Both chromosomes will express Xist in low concentrations, but then one chromosome will start to express high levels of Tsix, which dratically reduces the concentration of Xist on that chromosome and thus, that chromosome become the

Answer 52

Active X-chromosome

Question 53

The ability of one genotype to produce more than one phenotype when exposed to different environements

Answer 53

Phenotypic plasticity

Question 54

Environmental effects (such as diet or stress) on a phenotype may involve

Answer 54

Epigenetic changes in gene function

Question 55

Changes in chromatin marks and transcriptional networks associated with sustained neuronal activity, mood disorders, and addiciton

Answer 55

Adult Neuronal plasticity and neurogenesis

Question 56

Methylation of the agouti gene results inthe agouti mRNA being made briefly during development, before the agouti gene is then silenced for the remainder of the mouses life. This leads to a

Answer 56

Healthy brown mouse

Question 57

Non-methylation of the agouti gene results in the agouti gene being continually active, producing mRNA across the mouse's lifespan. This leads to a

Answer 57

Yellow mouse that develops obesity and diabetes during adulthood

Question 58

When a female yellow mouse (agouti gene unmethylated) was given a diet supplement during pregnancy and nursing with additional methyl groups, her offspring were

Answer 58

Mostly brown and healthy (agouti gene methylated and silenced)

Question 59

When a female yellow mouse (agouti gene unmethylated) was given no dietary supplements during pregnancy, her offspring were

Answer 59

Mostly yellow and unhealthy (agouti gene unmethylated and active)

Question 60

What are two methods to study changes in the epigenome?

Answer 60

1. ) Bisulfite conversion of DNA | 2. ) Methylation-sensitive restriction enzymes

Question 61

Converts cytidine to uridine if the citidine is NOT methylated

Answer 61

Bisulfite

Question 62

Following bisulfite conversion, the DNA strands are no longer complementary and a PCR primer is generated by a reverse transcriptase. Next we perform

Answer 62

PCR, DNA sequencing, or Methylation specific restriction enzyme digestion

Question 63

The C's that are not methylated are converted toU's. Then they are replicated by DNA polymerase and become

Answer 63

T's

Question 64

We can ditect DNA methylation using methylation-sensitive restriction enzymes. The methylation incensitive restriction enzymes will

Answer 64

Cut DNA next to a methylated C

Question 65

Functionally relevant changes to the genome that do not involve a change in nucleotide sequence

Answer 65

Epigenetics

Question 66

Epigenetics are cellular and physiological traits that ARE heritable by daughter cells and not cause by changes in

Answer 66

DNA sequence

Question 67

Epigenetics describes the study of stable, usually long-term alterations in the

Answer 67

Transcriptional potential of a cell

Question 68

These covalent modifications alter how genes are expressed without altering the underlying DNA sequence -an example of epigenetics

Answer 68

1. ) DNA methylation | 2. ) Histone modifications

Question 69

Attach to silencer regions of the DNA and remain associated with the silencer regions subsequent to DNA replication and cell division

Answer 69

Repressor proteins

Question 70

Epigenetics may last through cell divisions for the duration of a cell's lie and may also last for multiple generations. These non-genetic factors cause the organisms genes to

Answer 70

Behave (or "express themselves") differently

Question 71

Methylation of Cytosine can turn off

Answer 71

Gene expression

Question 72

Methylation of CpG in 98% of the genome does not matter. But methylation of the CpG stretches before transcriptional start site,

Answer 72

Inactivates transcription

Question 73

If there is an MeCP2 mutation in a boy, they will likely die as a fetus girls survive due to the fact that they have

Answer 73

Two X-Chromosomes

Question 74

Inactivation of one of the X-chromosomes is called

Answer 74

Lyonization

Question 75

Once you use a methylation-sensitive restriction enzyme technique, you can study the results with

Answer 75

Southern-blot hybridization