Exam 5: Epigenetic Phenomena

Question 1

5-azacytidine

Answer 1

DNA methyltransferase (DNMT) inhibitor that causes hypomethylation of the genome
potential to counteract malignancies associated with hypermethylation
therapy for acute myeloid leukemia

Question 2

Angelman syndrome (AS)

Answer 2

caused by deletion on maternal chromosome 15
unusual facial features, seizures, movement and gait disorders, severe mental retardation
(parent of origin effect)

Question 3

Beckwith-Wiedemann Syndrome (BWS)

Answer 3

uniparental disomy
child inherits both homologues of a portion of chromsome 11 from father
overabundance of insulin-like growth factor 2 - leads to kidney, adrenal, and liver problems resulting in severe hypoglycemia
susceptibility to childhood cancer

Question 4

Boundary elements

Answer 4

chromatin barriers
separates active and inactive genomic regions - stops spread of inactivation region caused by cytosine methylation self-propagation

Question 5

chromatin barriers

Answer 5

boundary elements
stop spread of inactivated region of DNA (caused by cytosine methylation) and separates active and inactive genomic regions

Question 6

CpG islands

Answer 6

clusters of CpG dinucleotide repeats close to 5’ region of genes
generally unmethylated
CpG dinucleotide repeats are very susceptible to methylation - methylation of CpG islands shut down expression of neighboring genes

Question 7

CpG dinucleotide repeat

Answer 7

very susceptible to methylation on cytosine residues - silences chromosomal region
about 70% in human genome are silenced by methylation - includes highly repetitive DNA, telomeres, and centromeres

Question 8

de-novo DNA methylation

Answer 8

methylation of unmethylated cytosine bases of DNA

introduced into unmethylated strand of DNA by DNA methyltransferases DNMT3a and b

Question 9

DNA methyltransferase (DNMT) inhibitors

Answer 9

inhibitor that causes hypomethylation of genome - counteracts malignancies associated with hypermethylation
therapy for acute myeloid leukemia
5-azacytidine

Question 10

DNA methyltransferase DNMT1

Answer 10

maintains pattern of DNA methylation throughout mitosis
during DNA replication, non-methylated strand is synthesized on methylated template strand
non-methylated strand is methylated by DNMT1

Question 11

epigenetics

Answer 11

study of stable, heritable changes in gene expression that do not involve changes in DNA sequence
important for: imprinting during development & gametogenesis, inactivation of X-chromosome, and progression of cancer

Question 12

genomic instability

Answer 12

can be caused by hypomethylation (de-methylation of silent chromatin) - initiating transformation of a cell into a tumor cell
leads to somatic recombination - Non-homologous recombination
leads to drastic increase in mutations in established tumor

Question 13

histone acetyltransferases (HATs)

Answer 13

acetylates histones, decreasing their binding affinity to DNA and facilitates transcription
Histone modification

Question 14

histone de-acetylase (HDAC) inhibitors

Answer 14

promote histone hyperacetylation and gene re-expression in chronic lymphocytic leukemia

Question 15

hypomethylation

Answer 15

lead to expression of genes in normally silent regions of genome
leads to re-expression of silenced genes and expression of endogenous retroviruses
reactivate transposable elements - leads to somatic recombination and genomic instability

Question 16

histone deacetylases (HDACs)

Answer 16

remove acetyl groups from histones
favors binding of histones to DNA (increases binding affinity), leading to chromatin condensation & silencing of transcription

Question 17

histone methylases

Answer 17

bind to HP1 proteins that are bound to methylated histones (after de-acetylation of histones)
methylation of histones spread long chromosomes until a boundary element is reached
methylases allow chromatin inactivation to spread

Question 18

HP1 proteins

Answer 18

bind to methylated histones after histones have been de-acetylated
bind histone methylases to spread chromatin inactivation

Question 19

hypermethylation

Answer 19

shuts down expression of genes close to CpG islands
silences gene transcription
may cause cancer by silencing tumor suppressor genes

Question 20

maintenance of DNA methylation

Answer 20

maintained through mitosis by DNA methyltransferase DNMT1 by methylating non-methylated strand after DNA replication

Question 21

methylcytosine binding proteins (MBPs)

Answer 21

binding brings about repression of transcription
occurs after a stretch of DNA has been methylated by DNA methyltransferases
interact with repressors of transcription (blocks transcription of nearby genes) & histone deacetylases (HDACs) (remove acetyl groups from histones leading to chromatin condensation/inactivation of transcription)

Question 22

parent of origin effect

Answer 22

inheritance of genetic variation from the mother or father

certain genes expressed due to imprinting - phenotypic variation

Question 23

Prader-Willi syndrome (PWS)

Answer 23

deletion on paternal chromosome 15
characterized by obesity, excessive food seeking behavior, hypogonadism and mental retardation
(parent of origin effect)

Question 24

retrotransposons in human genome

Answer 24

transcriptionally inactive DNA
mobile genetic elements that could cause mutations/disease if not silenced by methylation
about 45% of human genome derived from retrotransposons of viral origin
silenced by methylation

Question 25

uniparental disomy

Answer 25

abnormality where rescue of an aneuploid zygote where surplus chromosome is lost & rescued zygote retains both chromosomes from same parent
can lead to a situation in which an individual has only maternally or only paternally imprinted homologues of a chromosome
Can lead to problems with gene dosage - overabundance on one gene and lack of another

Question 26

X-chromosome inactivating center (XIC)

Answer 26

contains XIST (inactive X-specific transcript) gene - gets transcribed on X-chromosome to be inactivated
inactivation of X-chromosome proceeds via imprinting

Question 27

XIST (inactive X-specific transcript)

Answer 27

in XIC of X-chromosome, gene transcribed on X-chromosome to be inactivated
RNA associates closely with X-chromosome and mediates inactivation of most of the chromsome
DNA and histones on X chromosome to be inactivated are methylated - shuts down expression of most genes

Question 28

heterochromatin

Answer 28

tightly packed DNA - histones are deacetylated & methylated, DNA methylated - transcription silenced

Question 29

euchromatin

Answer 29

loosely packed DNA - histones acetylated, DNA not methylated - transcriptionally active

Question 30

imprinting

Answer 30

form of DNA silencing, shuts down certain chromosome regions & maintained throughout mitosis
marks chromosome as having come from father or mother - some genes are repressed of maternal chromosome while others of paternal
takes place during gametogenesis - imprinting center (silences chromosomal regions by DNA methylation and histone deacetylation)

Question 31

Imprinting important in 2 biological processes:

Answer 31

Development - cell type specific imprint established
Maturation of gametes - gametogenesis, parent of origin specific imprint imposed on chromosomes (make all inherited chromosomes look either maternal or paternal)

Question 32

Cancer can result from hypo or hypermethylation by:

Answer 32

hypomethylation - demethylation (& overexpression) of oncogenes, expression of silent chromatin - somatic recombination, increase in mutations
hypermethylation - silencing of tumor suppressor genes