1What does epigenetics study?
Regulation of gene activity without changing the underlying DNA sequence.
Slide 1: Introduction to Epigenetics
2Why can nerve and muscle cells behave differently despite similar DNA?
They express different sets of genes, partly due to epigenetic regulation.
Slide 1: Introduction to Epigenetics
3Name three major layers of epigenetic regulation.
DNA methylation, histone modifications, and chromatin organization.
Slide 1: Introduction to Epigenetics
4What does “Anything but ATCG” mean in epigenetics?
Regulatory information beyond the sequence of the four DNA bases.
Slide 2: Epigenetics
5What does epigenetic stability allow?
Maintenance of gene-activity patterns across cell divisions.
Slide 2: Epigenetics
6What does epigenetic reversibility mean?
A cell can change an established epigenetic state when needed.
Slide 2: Epigenetics
7What is a knockout (KO) embryo?
An embryo in which a specific gene has been inactivated or removed.
Slide 3: Why Epigenetics Matters
8Which three epigenetic regulators are compared in the embryo examples?
Eed, Dnmt1, and G9a.
Slide 3: Why Epigenetics Matters
9What do knockout experiments with Eed, Dnmt1, or G9a demonstrate?
Key epigenetic regulators are required for normal embryonic development.
Slide 3: Why Epigenetics Matters
10What is gastrulation?
An early embryonic process establishing the basic body layers.
Slide 3: Why Epigenetics Matters
11What type of epigenetic drug is romidepsin?
A histone deacetylase inhibitor (HDAC inhibitor).
Slide 4: Clinical Opportunities
12What enzymatic activity do HDAC inhibitors block?
Removal of acetyl groups from histone proteins.
Slide 4: Clinical Opportunities
13Which cancer is shown in the romidepsin clinical example?
Cutaneous T-cell lymphoma.
Slide 4: Clinical Opportunities
14What does the romidepsin example illustrate?
Targeting an epigenetic enzyme can produce a clinical treatment response.
Slide 4: Clinical Opportunities
15What is chromatin accessibility?
How easily proteins can reach and interact with a DNA region.
Slide 5: All Layers Act Together to Orchestrate Selective Accessibility
16Which structural levels jointly influence chromatin accessibility?
Nucleosomes, chromatin domains/loops, and nuclear organization.
Slide 5: All Layers Act Together to Orchestrate Selective Accessibility
17Why is 3D genome position relevant to gene activity?
It can influence which DNA regions and regulatory elements interact.
Slide 5: All Layers Act Together to Orchestrate Selective Accessibility
18What chemical group is added during DNA methylation?
A methyl group (–CH₃).
Slide 6: DNA Methylation
19Which base is mainly methylated in the mammalian examples?
Cytosine.
Slide 6: DNA Methylation
20What does 5mC stand for?
5-methylcytosine: cytosine methylated at carbon position five.
Slide 6: DNA Methylation
21What enzymes add methyl groups to DNA?
DNA methyltransferases (DNMTs).
Slide 6: DNA Methylation
22Does adding a methyl group to cytosine change DNA base pairing?
No. Methylated cytosine still pairs with guanine.
Slide 7: DNA Methylation Does Not Change the Coding Sequence
23How does DNA methylation differ from a genetic mutation?
Methylation changes a base’s chemical state; a mutation changes DNA sequence.
Slide 7: DNA Methylation Does Not Change the Coding Sequence
24Can methylated DNA regulate gene activity without changing its sequence?
Yes. The modification can alter DNA–protein interactions.
Slide 7: DNA Methylation Does Not Change the Coding Sequence
25What is a CpG dinucleotide?
A cytosine followed by guanine on the same DNA strand.
Slide 8: DNA Methylation Targets the CpG Dinucleotide
26What does the “p” in CpG represent?
The phosphate linkage between the two nucleotides.
Slide 8: DNA Methylation Targets the CpG Dinucleotide
27About how many CpG sites are in a human haploid genome, per the slides?
Approximately 28 million.
Slide 8: DNA Methylation Targets the CpG Dinucleotide
28About how many cytosines are in a human haploid genome, per the slides?
Approximately 580 million.
Slide 8: DNA Methylation Targets the CpG Dinucleotide
29Why can CpG methylation be symmetrical?
Complementary DNA strands both have cytosines in a CpG context.
Slide 8: DNA Methylation Targets the CpG Dinucleotide
30What is deamination?
Removal of an amino group from a molecule.
Slide 9: Deamination
31What base results from deamination of ordinary cytosine?
Uracil.
Slide 9: Deamination
32Why does uracil in DNA often trigger repair?
Uracil is not normally a DNA base, so it signals damage.
Slide 9: Deamination
33What approximate deamination frequency is mentioned on the slide?
About 100 events per cell per day in the illustrated context.
Slide 9: Deamination
34What does deamination of adenine produce?
Hypoxanthine.
Slide 10: Unnatural DNA Bases
35What does deamination of guanine produce?
Xanthine.
Slide 10: Unnatural DNA Bases
36Why is deamination of 5-methylcytosine especially problematic?
It produces thymine, a normal DNA base, complicating damage recognition.
Slide 10: Unnatural DNA Bases
37What does 5-methylcytosine become after deamination?
Thymine.
Slide 11: DNA Methylation Targets the CpG Dinucleotide and Causes Its Depletion
38Why are CpG sites depleted over evolutionary time?
Deamination of 5mC can cause C-to-T mutations that are not always repaired.
Slide 11: DNA Methylation Targets the CpG Dinucleotide and Causes Its Depletion
39Why is a deaminated 5mC harder to detect than deaminated C?
It becomes normal thymine rather than unusual uracil.
Slide 11: DNA Methylation Targets the CpG Dinucleotide and Causes Its Depletion
40What is non-CpG DNA methylation?
Methylation of cytosine outside the CpG sequence context.
Slide 12: Cytosine Methylation
41What does H mean in CHG and CHH methylation?
Any base except guanine: A, C, or T.
Slide 12: Cytosine Methylation
42Which cells show notable non-CpG methylation in the slide?
Embryonic stem cells and induced pluripotent stem cells.
Slide 12: Cytosine Methylation
43What happens to non-CpG methylation during differentiation in the graph?
It decreases markedly.
Slide 12: Cytosine Methylation
44Which enzyme family is linked to non-CpG methylation levels?
DNMT3 de novo DNA methyltransferases.
Slide 12: Cytosine Methylation
45Why is CpG methylation well suited to maintenance after replication?
Its symmetric context provides a methylated complementary template.
Slide 13: Non-CpG DNA Methylation
46Why is non-CpG methylation often less straightforward to copy?
It lacks an equivalent symmetric methylatable site on the opposite strand.
Slide 13: Non-CpG DNA Methylation
47What is hemimethylated CpG DNA?
DNA methylated on one strand but not the complementary strand.
Slide 13: Non-CpG DNA Methylation
48What activity is particularly important for non-CpG methylation?
De novo methylation by DNMT3 enzymes.
Slide 14: Non-CpG DNA Methylation
49Where may high non-CpG methylation accumulate?
In selected non-dividing cells with current or earlier de novo methylation activity.
Slide 14: Non-CpG DNA Methylation
50Is non-CpG methylation equally abundant in every tissue?
No. It is enriched in selected cell types.
Slide 14: Non-CpG DNA Methylation
51What is an enzyme’s catalytic domain?
The structural region responsible for the chemical reaction.
Slide 15: Highly Conserved Catalytic Domain
52What does structural similarity between DNMT2 and bacterial M.HhaI suggest?
Evolutionary conservation of methyltransferase-related catalytic architecture.
Slide 15: Highly Conserved Catalytic Domain
53Does a conserved catalytic fold guarantee identical biological substrates?
No. Similar structures can support different biological functions.
Slide 15: Highly Conserved Catalytic Domain
54What is DNMT1’s main function?
Maintenance of DNA methylation after replication.
Slide 16: DNA Methylation and the Enzymes Are Essential
55What are the main de novo DNA methyltransferases in mammals?
DNMT3A and DNMT3B.
Slide 16: DNA Methylation and the Enzymes Are Essential
56What is DNMT3L’s main role?
It supports other methyltransferases but lacks normal catalytic activity.
Slide 16: DNA Methylation and the Enzymes Are Essential
57What can occur when key methyltransferase genes are knocked out?
Severe developmental defects and, in some cases, embryonic lethality.
Slide 16: DNA Methylation and the Enzymes Are Essential
58What molecule donates methyl groups to DNA methyltransferases?
S-adenosylmethionine (SAM).
Slide 17: Methyl-Group Transfer
59Which atom of cytosine receives the methyl group?
Carbon position five.
Slide 17: Methyl-Group Transfer
60What catalytic residue type participates in the DNMT reaction?
A conserved cysteine residue.
Slide 17: Methyl-Group Transfer
61What is the product of methylation of cytosine by a DNMT?
5-methylcytosine (5mC).
Slide 17: Methyl-Group Transfer
62What is UHRF1’s role in DNA methylation maintenance?
It recognizes hemimethylated DNA and helps recruit DNMT1.
Slide 18: DNMT1 Needs a Cofactor
63Why does hemimethylated DNA appear after replication?
The original strand is methylated, while the newly made strand is not yet methylated.
Slide 18: DNMT1 Needs a Cofactor
64What does DNMT1 do after UHRF1 binds hemimethylated DNA?
Methylates matching CpG cytosines on the new strand.
Slide 18: DNMT1 Needs a Cofactor
65What happens when UHRF1 function is lost?
Maintenance methylation is severely impaired, with major methylation loss.
Slide 18: DNMT1 Needs a Cofactor
66What is passive DNA demethylation?
Loss of methylation over DNA replications when maintenance methylation fails.
Slide 19: Removing the Methyl Group: What Are the Options?
67What is active DNA demethylation?
Chemical modification and/or DNA repair that removes methylation information.
Slide 19: Removing the Methyl Group: What Are the Options?
68Why does passive demethylation depend on cell division?
Replication dilutes methylation if new strands are not remethylated.
Slide 19: Removing the Methyl Group: What Are the Options?
69Which enzymes oxidize 5-methylcytosine during active demethylation?
TET enzymes.
Slide 20: Potential Pathways to Create Unmethylated Cytosine
70What is the first oxidation product of 5mC?
5-hydroxymethylcytosine (5hmC).
Slide 20: Potential Pathways to Create Unmethylated Cytosine
71What product follows 5hmC in the TET oxidation sequence?
5-formylcytosine (5fC).
Slide 20: Potential Pathways to Create Unmethylated Cytosine
72What product follows 5-formylcytosine in the TET pathway?
5-carboxylcytosine (5caC).
Slide 20: Potential Pathways to Create Unmethylated Cytosine
73Which repair-related enzyme can remove oxidized cytosines?
Thymine DNA glycosylase (TDG).
Slide 20: Potential Pathways to Create Unmethylated Cytosine
74What does BER stand for?
Base excision repair; it can restore unmodified cytosine.
Slide 20: Potential Pathways to Create Unmethylated Cytosine
75Name the three mammalian TET proteins.
TET1, TET2, and TET3.
Slide 21: Potential Pathways to Create Unmethylated Cytosine
76What does the CXXC domain help recognize?
CpG-rich DNA regions.
Slide 21: Potential Pathways to Create Unmethylated Cytosine
77Which metal cofactor is important for TET catalytic activity?
Iron in the Fe(II) state.
Slide 21: Potential Pathways to Create Unmethylated Cytosine
78Do TET1, TET2, and TET3 have identical domain organization?
No. They share catalytic machinery but differ in some domains.
Slide 21: Potential Pathways to Create Unmethylated Cytosine
79What is a CpG island?
A genomic region enriched in CpG dinucleotides.
Slide 22: DNA Methylation
80How are many promoter CpG islands methylated in normal cells?
They are usually largely unmethylated.
Slide 22: DNA Methylation
81What are cis-regulatory elements (CREs)?
DNA regions, such as enhancers, that influence gene transcription.
Slide 22: DNA Methylation
82Why are repetitive DNA elements often methylated?
Methylation can help limit unwanted repetitive-element activity.
Slide 22: DNA Methylation
83What happens to DNA methylation during preimplantation development?
The genome undergoes extensive methylation reorganization and broad reduction.
Slide 23: DNA Methylation in Development: Preimplantation Dynamics
84What is the inner cell mass (ICM)?
The cell population within the blastocyst that contributes to the embryo.
Slide 23: DNA Methylation in Development: Preimplantation Dynamics
85Does preimplantation demethylation affect all genomic regions equally?
No. Different regions show different methylation trajectories.
Slide 23: DNA Methylation in Development: Preimplantation Dynamics
86What happens to many DNA methylation levels after implantation?
They increase as characteristic somatic patterns are established.
Slide 24: DNA Methylation in Development: Preimplantation and Postimplantation
87What is the epiblast?
An embryonic cell population that contributes to the future embryo.
Slide 24: DNA Methylation in Development: Preimplantation and Postimplantation
88Is postimplantation DNA methylation uniform across the genome?
No. CpG islands and regulatory regions can remain locally unmethylated.
Slide 24: DNA Methylation in Development: Preimplantation and Postimplantation
89What are focal DNA methylation changes?
Changes restricted to particular genomic sites, not the whole genome.
Slide 25: Focal Dynamics at Enhancers
90Why are enhancer methylation patterns useful for identifying cell identity?
Enhancers can have cell-type-specific epigenetic states.
Slide 25: Focal Dynamics at Enhancers
91What is an enhancer?
A regulatory DNA sequence that can influence transcription of a gene.
Slide 25: Focal Dynamics at Enhancers
92Which mark is especially associated with active promoters in the slides?
H3K4me3.
Slide 25: Focal Dynamics at Enhancers
93What does H3K27me3 mean?
Trimethylation of lysine 27 on histone H3.
Slide 26: Repression of CpG Island Promoters: H3K27me3
94What regulatory role is H3K27me3 generally associated with?
Polycomb-associated transcriptional repression.
Slide 26: Repression of CpG Island Promoters: H3K27me3
95Must CpG island promoters be DNA-methylated to be repressed?
No. Histone-based repression, including H3K27me3, can silence them.
Slide 26: Repression of CpG Island Promoters: H3K27me3
96Why can DNA methylation patterns serve as biomarkers?
Different tissues and cell states have characteristic methylation profiles.
Slide 27: DNA Methylation: Focal Dynamics
97What does a DNA methylation heatmap color scale of 0 to 1 mean?
It represents 0% to 100% methylation.
Slide 27: DNA Methylation: Focal Dynamics
98What can methylation patterns help identify in an unknown sample?
Its likely cell or tissue origin.
Slide 27: DNA Methylation: Focal Dynamics
99When does strong methylation reprogramming occur in development?
During germ-cell development and early embryogenesis.
Slide 28: Global Dynamics
100What does PGC stand for?
Primordial germ cell.
Slide 28: Global Dynamics
101How does methylation generally change after the early embryonic low point?
It rises as somatic cell methylation patterns are established.
Slide 28: Global Dynamics
102Do placenta, somatic tissues, and tumors always share the same global methylation?
No. The slide shows different global methylation states.
Slide 28: Global Dynamics
103What is an epigenetic alteration in a tumor?
An abnormal regulatory state, such as a changed DNA methylation pattern.
Slide 29: Epigenetic Alterations in Tumors
104Why compare tumor and healthy-tissue methylation profiles?
To identify disease-associated methylation differences.
Slide 29: Epigenetic Alterations in Tumors
105Do cancer-associated changes have to be DNA sequence mutations?
No. Tumors can also acquire epigenetic abnormalities.
Slide 29: Epigenetic Alterations in Tumors
106What is epigenetic convergence in cancer?
Different tumors developing some similar epigenetic changes.
Slide 30: Epigenetic Alterations in Tumors
107Why might shared epigenetic changes across tumors be useful?
They may point to common disease mechanisms or possible targets.
Slide 30: Epigenetic Alterations in Tumors
108Are all epigenetic alterations shared between tumor types?
No. Many changes remain tumor-type-specific.
Slide 30: Epigenetic Alterations in Tumors
109How does DNA methylation distribution differ between many invertebrates and vertebrates?
Invertebrates often show more selective methylation; vertebrates more widespread methylation.
Slide 31: Schübeler, Nature 2015
110Which vertebrate promoter regions are commonly protected from methylation?
CpG island promoters.
Slide 31: Schübeler, Nature 2015
111Why should DNA methylation patterns not be assumed universal across species?
Their genomic distributions and regulatory roles vary between organism groups.
Slide 31: Schübeler, Nature 2015
112What changes first in the presented differentiation time course: mRNA or promoter methylation?
mRNA expression decreases before strong promoter methylation appears.
Slide 32: Repression by DNA Methylation Is Generally a Secondary Event
113What does this timing suggest about promoter DNA methylation?
It can stabilize gene repression after repression has begun.
Slide 32: Repression by DNA Methylation Is Generally a Secondary Event
114Why does this slide challenge “methylation always causes gene silencing”?
In its example, expression falls before methylation rises substantially.
Slide 32: Repression by DNA Methylation Is Generally a Secondary Event
115What does COAD stand for?
Colon adenocarcinoma.
Slide 33: Shared Epigenetic Alterations
116What does READ stand for?
Rectal adenocarcinoma.
Slide 33: Shared Epigenetic Alterations
117What does LUAD stand for?
Lung adenocarcinoma.
Slide 33: Shared Epigenetic Alterations
118How many shared features are shown for COAD and READ?
885 shared features.
Slide 33: Shared Epigenetic Alterations
119How many shared features are shown for LUAD and COAD?
521 shared features.
Slide 33: Shared Epigenetic Alterations
120What do the overlap diagrams illustrate?
Tumors have both shared and cancer-type-specific epigenetic changes.
Slide 33: Shared Epigenetic Alterations
121What is chromatin?
DNA packaged with histones and associated proteins.
Slide 34: The Epigenome Has Multiple Layers
122What three epigenetic layers are emphasized here?
DNA modifications, histone-based packaging, and higher-order chromatin structure.
Slide 34: The Epigenome Has Multiple Layers
123What is the fundamental repeating unit of chromatin?
The nucleosome.
Slide 34: The Epigenome Has Multiple Layers
124What is a nucleosome?
DNA wrapped around a histone octamer.
Slide 35: Nucleosomes: The Histone Octamer
125Which four histones form the core octamer?
H2A, H2B, H3, and H4, with two copies of each.
Slide 35: Nucleosomes: The Histone Octamer
126What are histone tails?
Flexible protein regions projecting from nucleosomes and carrying modifications.
Slide 35: Nucleosomes: The Histone Octamer
127What does PTM stand for in histone biology?
Post-translational modification.
Slide 35: Nucleosomes: The Histone Octamer
128Are nucleosomes only passive DNA packaging units?
No. Their composition and modifications influence regulation.
Slide 35: Nucleosomes: The Histone Octamer
129What is a histone variant?
An alternative form of a histone protein with distinct properties.
Slide 36: Histone Variants
130Which histone variant is associated with active chromatin?
H3.3.
Slide 36: Histone Variants
131Which H2A variant is linked to DNA double-strand-break responses?
H2A.X.
Slide 36: Histone Variants
132Which H2A variant is highly conserved among eukaryotes?
H2A.Z.
Slide 36: Histone Variants
133Why do histone variants matter?
They diversify nucleosome properties and chromatin functions.
Slide 36: Histone Variants
134Name three types of histone post-translational modification.
For example: acetylation, methylation, and phosphorylation.
Slide 37: Overview of Histone Modifications
135Which amino acid is often acetylated on histones?
Lysine.
Slide 37: Overview of Histone Modifications
136Which residues are commonly methylated on histones?
Lysine and arginine.
Slide 37: Overview of Histone Modifications
137Which two histone modifications are a major focus of these slides?
Acetylation and methylation.
Slide 37: Overview of Histone Modifications
138Is histone acetylation generally associated with active or repressed chromatin?
It is commonly associated with active chromatin.
Slide 38: Overview of Histone Modifications
139Does histone methylation always mean gene repression?
No. The effect depends on the residue and methylation state.
Slide 38: Overview of Histone Modifications
140Why does the combination of histone marks matter?
Different combinations are associated with distinct regulatory chromatin states.
Slide 38: Overview of Histone Modifications
141What is the histone code hypothesis?
Histone modifications may act in combinations to direct biological outcomes.
Slide 39: A Histone (Modification) Code?
142Is a single histone modification always enough to predict gene activity?
No. Its function depends on context and other modifications.
Slide 39: A Histone (Modification) Code?
143Is the histone code completely understood?
No. Its combinations and interpretations remain complex.
Slide 39: A Histone (Modification) Code?
144What happens to lysine’s positive charge after acetylation?
The positive charge is neutralized.
Slide 40: Effects of Lysine Acetylation
145Why can histone acetylation weaken DNA–histone interactions?
It reduces positive histone charge interacting with negative DNA.
Slide 40: Effects of Lysine Acetylation
146What are KATs?
Lysine acetyltransferases that add acetyl groups.
Slide 40: Effects of Lysine Acetylation
147What are HDACs?
Histone deacetylases that remove acetyl groups.
Slide 40: Effects of Lysine Acetylation
148Is histone acetylation reversible?
Yes. KATs and HDACs control addition and removal.
Slide 40: Effects of Lysine Acetylation
149How many methyl groups can a lysine residue receive?
One, two, or three (me1, me2, or me3).
Slide 41: Histone Methylation
150What methylation states can arginine have?
Monomethylated or dimethylated.
Slide 41: Histone Methylation
151How does a histone methylation mark’s function depend on its position?
Different residues can be linked to activation, repression, or other functions.
Slide 41: Histone Methylation
152How many histone methylation sites does the slide report?
At least 24 across core histone proteins.
Slide 41: Histone Methylation
153What is an epigenetic “writer”?
An enzyme that adds a chromatin modification.
Slide 42: Sites of Histone Methylation
154What is an epigenetic “reader”?
A protein that recognizes a particular chromatin modification.
Slide 42: Sites of Histone Methylation
155What is an epigenetic “eraser”?
An enzyme that removes a chromatin modification.
Slide 42: Sites of Histone Methylation
156Which type of enzyme writes histone methylation?
A histone methyltransferase.
Slide 42: Sites of Histone Methylation
157Which type of enzyme erases histone methylation?
A histone demethylase.
Slide 42: Sites of Histone Methylation
158In which organism was Polycomb first discovered?
The fruit fly Drosophila.
Slide 43: Polycomb
159What genes are historically regulated by Polycomb during development?
Homeotic genes controlling body-region identity.
Slide 43: Polycomb
160What can loss of Polycomb regulation cause?
Developmental patterning defects due to incorrect gene expression.
Slide 43: Polycomb
161What is the main regulatory role of Polycomb proteins?
Helping maintain repression of selected genes.
Slide 43: Polycomb
162What does PcG stand for?
Polycomb group.
Slide 44: Polycomb Group (PcG) Proteins
163What does PRC stand for?
Polycomb repressive complex.
Slide 44: Polycomb Group (PcG) Proteins
164What are the two main families of Polycomb complexes?
PRC1 and PRC2.
Slide 44: Polycomb Group (PcG) Proteins
165What is BMI1 also called?
PCGF4, a Polycomb group RING finger protein.
Slide 44: Polycomb Group (PcG) Proteins
166Which PRC2 protein provides H3K27 methyltransferase activity?
EZH2.
Slide 45: Polycomb Repressive Complexes
167Which other core components are highlighted in PRC2?
EED and SUZ12.
Slide 45: Polycomb Repressive Complexes
168Which histone modification is connected to PRC2 activity?
H3K27me3.
Slide 45: Polycomb Repressive Complexes
169Which histone modification is linked to PRC1 activity?
Ubiquitination of histone H2A.
Slide 45: Polycomb Repressive Complexes
170Do all PRC1/PRC2 assemblies have identical protein composition?
No. Canonical, variant, and alternative complexes have differing components.
Slide 45: Polycomb Repressive Complexes
171Why does Polycomb complex composition matter?
Different protein combinations affect complex function and regulation.
Slide 46: Polycomb Group (PcG) Proteins
172What is meant by a multimeric Polycomb complex?
An assembly of several proteins acting together.
Slide 46: Polycomb Group (PcG) Proteins
173What does PCGF stand for?
Polycomb group RING finger protein family.
Slide 46: Polycomb Group (PcG) Proteins
174What do EZH2 catalytic inhibitors aim to block?
EZH2-mediated methylation of histone H3K27.
Slide 47: Targeting Polycomb Complexes
175How does a protein degrader differ from an enzyme inhibitor?
A degrader promotes protein removal; an inhibitor blocks an activity.
Slide 47: Targeting Polycomb Complexes
176Which PRC2 protein–protein interaction is targeted in the schematic?
The EZH2–EED interaction.
Slide 47: Targeting Polycomb Complexes
177Name two strategies for targeting PRC2.
Catalytic inhibition and targeted protein degradation.
Slide 47: Targeting Polycomb Complexes
178Which PRC2-associated proteins are shown as drug targets?
EZH2 and EED.
Slide 47: Targeting Polycomb Complexes
179What is a genomic data track?
A measurement plotted along genomic coordinates.
Slide 48: Actively Transcribed Regions
180Which histone mark often highlights active promoters?
H3K4me3.
Slide 48: Actively Transcribed Regions
181Which mark is associated with active promoters and enhancers?
H3K27ac.
Slide 48: Actively Transcribed Regions
182Why analyze several epigenomic tracks together?
Each reveals a different part of regulatory activity.
Slide 48: Actively Transcribed Regions
183What is NANOG associated with in embryonic stem cells?
Pluripotency.
Slide 49: Actively Transcribed Regions: HUES64 Human Embryonic Stem Cells
184What does pluripotency mean?
Ability to develop into many different cell types.
Slide 49: Actively Transcribed Regions: HUES64 Human Embryonic Stem Cells
185Which pluripotency-related transcription factors appear in the figure?
NANOG, OCT4, and SOX2.
Slide 49: Actively Transcribed Regions: HUES64 Human Embryonic Stem Cells
186What information does H3K36me3 commonly provide?
It is associated with actively transcribed gene regions.
Slide 49: Actively Transcribed Regions: HUES64 Human Embryonic Stem Cells
187What is HUES64 in the figure?
A human embryonic stem cell line.
Slide 49: Actively Transcribed Regions: HUES64 Human Embryonic Stem Cells
188Why is the linear DNA sequence insufficient to explain all regulation?
Distant DNA elements may be physically close in 3D chromatin.
Slide 50: 2D to 3D
189What type of long-range interaction is central to this slide?
Enhancer–promoter contact through chromatin folding.
Slide 50: 2D to 3D
190What does the slide title “2D to 3D” emphasize?
Moving from linear genome tracks to spatial genome organization.
Slide 50: 2D to 3D
191What is heterochromatin?
Relatively compact chromatin, often associated with reduced transcription.
Slide 51: Organization of the Nucleus
192What is euchromatin?
Less compact chromatin, generally more accessible to transcription machinery.
Slide 51: Organization of the Nucleus
193How does heterochromatin appear in the electron micrograph?
As comparatively dark, dense nuclear regions.
Slide 51: Organization of the Nucleus
194What is the nucleolus mainly involved in?
Ribosomal RNA production and ribosome assembly.
Slide 51: Organization of the Nucleus
195Where is inactive chromatin often enriched within a nucleus?
Near the nuclear periphery.
Slide 52: Organization of the Nucleus
196Where is active chromatin often located in the schematic?
More toward the nuclear interior.
Slide 52: Organization of the Nucleus
197Does nuclear position alone determine whether every gene is active?
No. These are general tendencies, not absolute rules.
Slide 52: Organization of the Nucleus
198What does Xa mean in X-chromosome diagrams?
An active X chromosome.
Slide 53: Nuclear Organization and X-Chromosome Inactivation
199What does Xi mean in X-chromosome diagrams?
An inactive X chromosome.
Slide 53: Nuclear Organization and X-Chromosome Inactivation
200What is X-chromosome inactivation?
Epigenetic silencing of one X chromosome in cells with two X chromosomes.
Slide 53: Nuclear Organization and X-Chromosome Inactivation
201At what scale can X inactivation alter gene regulation?
Across almost an entire chromosome.
Slide 53: Nuclear Organization and X-Chromosome Inactivation
202What is a chromosome territory?
The nuclear region predominantly occupied by one chromosome.
Slide 54: Chromosome 19 and Chromosome 18
203Which is relatively gene-rich: chromosome 18 or 19?
Chromosome 19.
Slide 54: Chromosome 19 and Chromosome 18
204Which chromosome tends to be more peripheral: 18 or 19?
Chromosome 18, which is relatively gene-poor.
Slide 54: Chromosome 19 and Chromosome 18
205Which chromosome tends to lie more internally: 18 or 19?
Chromosome 19, which is relatively gene-rich.
Slide 54: Chromosome 19 and Chromosome 18
206What does a chromatin-contact heatmap display?
Interaction frequencies between different genomic positions.
Slide 55: Integration to Understand Genome Regulation
207What does a darker region in the slide’s contact heatmap indicate?
Relatively stronger interactions between those DNA regions.
Slide 55: Integration to Understand Genome Regulation
208Why integrate chromatin-contact and histone-mark data?
To connect potential regulatory elements with their possible targets.
Slide 55: Integration to Understand Genome Regulation
209What does RCD stand for in the slide’s diagram?
Regulatory chromatin domain.
Slide 55: Integration to Understand Genome Regulation
210What does TAD stand for?
Topologically associating domain.
Slide 56: TADs and Human Disease
211How are contacts organized within a TAD?
DNA regions interact more often with each other than with outside regions.
Slide 56: TADs and Human Disease
212Why can deleting a TAD boundary cause disease?
It can permit abnormal enhancer–gene interactions.
Slide 56: TADs and Human Disease
213What is brachydactyly?
A developmental condition involving unusually short fingers.
Slide 56: TADs and Human Disease
214Must a disease-causing structural variant disrupt a coding sequence?
No. It may alter regulatory contacts without changing a gene’s code.
Slide 56: TADs and Human Disease
215Name four scales of genome organization in the summary diagram.
DNA marks, nucleosomes, chromatin domains, and chromosome territories.
Slide 57: DNA Methylation and Nuclear Organization
216What is a chromatin loop?
A folded DNA configuration bringing separated genomic regions together.
Slide 57: DNA Methylation and Nuclear Organization
217What is the major conclusion about genome regulation across scales?
Local chemical marks and large-scale architecture act together.
Slide 57: DNA Methylation and Nuclear Organization
218What is transgenerational epigenetic inheritance?
Transmission of epigenetic information affecting later generations.
Slide 58: Transgenerational Epigenetic Inheritance
219Why is transgenerational epigenetic inheritance difficult to establish?
Epigenetic patterns are extensively reset during germ-cell and early embryo development.
Slide 58: Transgenerational Epigenetic Inheritance
220Does the TIME magazine cover constitute experimental evidence?
No. It introduces the topic and public interest.
Slide 58: Transgenerational Epigenetic Inheritance
221What is genomic imprinting?
Gene expression that depends on whether the copy came from mother or father.
Slide 59: Genomic Imprinting
222How do the two parental copies of an imprinted gene often differ?
One copy is expressed while the other is epigenetically repressed.
Slide 59: Genomic Imprinting
223Which epigenetic mechanism is important in many imprinted genes?
DNA methylation.
Slide 59: Genomic Imprinting
224What does “parent-of-origin effect” mean?
The biological effect depends on which parent transmitted the allele.
Slide 59: Genomic Imprinting
225What is a liquid biopsy?
Analysis of biological material from a body fluid, often blood.
Slide 60: Liquid Biopsy
226What does cfDNA stand for?
Cell-free DNA: DNA fragments released into body fluids.
Slide 60: Liquid Biopsy
227How can methylation help identify the tissue origin of cfDNA?
Compare cfDNA methylation signatures with tissue reference profiles.
Slide 60: Liquid Biopsy
228What does deconvolution of a cfDNA sample aim to estimate?
Contributions from different cell or tissue types.
Slide 60: Liquid Biopsy
229What do blue and yellow indicate on the shown methylation atlas?
Blue indicates low methylation; yellow indicates high methylation.
Slide 60: Liquid Biopsy
230What is an epigenome browser used for?
Visualizing epigenetic and genomic measurements along DNA coordinates.
Slide 61: Epigenome Browsing
231Which two cell types are compared on the slide?
Embryonic stem (ES) cells and mouse embryonic fibroblasts (MEFs).
Slide 61: Epigenome Browsing
232Which mark in the browser is linked to Polycomb repression?
H3K27me3.
Slide 61: Epigenome Browsing
233Why is it useful to compare the same genomic region across cell types?
To detect cell-type-specific differences in chromatin state.
Slide 61: Epigenome Browsing
234What is the main goal of epigenome editing?
Changing regulation at a chosen DNA region without necessarily altering sequence.
Slide 62: Epigenome Editing
235How does epigenome editing differ from conventional genome editing?
It targets regulatory states rather than requiring DNA sequence changes.
Slide 62: Epigenome Editing
236What business funding figure is shown in the slide’s example?
US$57 million for Moonwalk Biosciences.
Slide 62: Epigenome Editing
237Does the funding headline prove a treatment is clinically effective?
No. It illustrates commercial interest, not clinical validation.
Slide 62: Epigenome Editing
238What is Cas9 in conventional CRISPR editing?
A guide-RNA-directed DNA-cutting enzyme.
Slide 63: Epigenome Editing
239What does dCas9 stand for?
Catalytically dead Cas9.
Slide 63: Epigenome Editing
240What important ability does dCas9 retain?
Guide-RNA-directed binding to a chosen DNA sequence.
Slide 63: Epigenome Editing
241Why is dCas9 useful for epigenome editing?
It can localize regulatory proteins without cutting DNA.
Slide 63: Epigenome Editing
242What is a dCas9 fusion protein?
dCas9 joined to another functional protein or regulatory domain.
Slide 63: Epigenome Editing
243Name one approach for recruiting regulatory activity with dCas9.
Direct protein fusion or RNA-mediated recruitment.
Slide 63: Epigenome Editing