Epigenetics

Question 1

Wet-lab method to determine precise nucleosome positioning and phasing

Answer 1

MNase-seq and MNase-chip

Question 2

Histones have ________ charged N-temrinal tails that interact with nearby nucleosomal DNA. This allows for higher order packing.

Answer 2

Positively

Question 3

What affect does histone acetylation have on DNA?

Answer 3

Opens it up
(-) negates (+) tail charges
Promotes tc

Question 4

What affect does histone methylation have on DNA?

Answer 4

Depends on where methylation occurs
K4: activated tc
K9: repressed tc

Question 5

Histone modifications have _____ peaks around promoters, and _____ peaks throughout gene.

Answer 5

Sharp (promoters)

Broad (throughout gene)

Question 6

Block deacetylation

Promote tc of tumor suppressor genes

Answer 6

HDAC inhibitors

Question 7

2 pathways to active tc through modifying histones / nucleosomes

Answer 7

HATs (histone acetylases)

ATP dependent remodeling complex (remodels nucleosomes)

Question 8

Cytosine ___________ at promoters leads to silencing of nearby genes.

Answer 8

methylation

Question 9

What are some roles of DNA methylation?

Answer 9

Tc silencing of promoters
Protecting genome from transposition repetitive elements and viral gene expression
Genomic imprinting
X inactivation
Tissue and developmental specific gene expression
Blocking binding to some TFs

Question 10

Responsible for de novo methylation (early in development)

Answer 10

Dnmt3a

Dnmt3b

Question 11

Responsible for maintenance methylation after DNA replication

Answer 11

Dnmt1

Question 12

Some genes are expressed only from the maternal genome or only from the paternal genome
Maintained by DNA methylation

Answer 12

Genomic imprinting

Question 13

DNA methylation writers

Answer 13

DNA methyl transferases (DNMT)
Dnmt1
Dnmt3a
Dnmt3b

Question 14

DNA methylation erasers

Answer 14

Tet family

passive erasing during cell division

Question 15

DNA methylation readers

Answer 15

Methyl binding domain proteins

MeCP2

Question 16

Identifies histone modification and protein-DNA binding sites

Cross link proteins to DNA, sonicate to shear, immunoprecipitate with Ab to TF/histone/histone modification, reverse cross links and sequence

Answer 16

ChIP

Chromatin Immunoprecipitation

Question 17

Active gene regulatory elements (promoters, enhancers, silencers, insulators, LCR, meiotic recombination hotspots) are DNase ___________

Answer 17

hypersensitive

tightly wrapped DNA more resistant to DNase

Question 18

Coding sequence mutation that disrupts chromatin regulator

MECP2 causes:

Answer 18

Rett syndrome

Question 19

Coding sequence mutation that disrupts chromatin regulator

CHD7 causes:

Answer 19

CHARGE syndrome

Question 20

Coding sequence mutation that disrupts chromatin regulator

H3F3A/HIST1H3B causes:

Answer 20

DIPG

Question 21

Noncoding mutations that impair gene regulation IGF2/H19 causes:

Answer 21

Beckwith-Wiedemann syndrome

Question 22

Noncoding mutations that impair gene regulation CACNA1C corresponds to:

Answer 22

Schizophrenia

Question 23

Loss impairs synaptic development in brain
Regulates long neuronal genes that are labeled by mCA (neurons accumulate on-CpG methlyatlion after birth)
Mutation leads to Rhett syndrome on X chromosome (affects mostly girls - mosaics, lethal in boys)
(neuron selectivity)

Answer 23

MeCP2

Question 24

Chromodomain helicase that remodels nucleosome architecture at regulatory elements
Mutation affects neural crest cell differentiation and migration, which leads to CHARGE
(phenotype variability)

Answer 24

CHD7

Question 25

Mutations in these histone genes lead to DIPG (diffuse intrinsic pontine glioma) Histone amino acid change (often from lys27 to met) Mutations leads to global depression of cancer promoting genes (regional specificity)

Answer 25

H3F3A | HIST1H3B

Question 26

Impaired methylation of imprinting control region regions (for IGF2/H19 domains) on chromosome 11p15.5 is associated with:

Answer 26

Beckwith-Wiedemann Syndrome

Question 27

Schizophrenia associated SNPs in ___________ enhancers impair tc of the calcium channel (mechanistic discovery)

Answer 27

CACNA1C

Question 28

Maternal care in mice influxes later ________ response via methylation of the glucocorticoid receptor gene Nr3c1 expression (vulnerability and resilience)

Answer 28

stress

Question 29

Feeding agouti mice dietary supplements results in _________ of the Avy transposon, reversing coat color (you are what you eat)

Answer 29

methylation