Iwafuchi 1 Flashcards

Flashcards for Iwafuchi Lecture 1 (80 cards)

1
Q

What is the approximate length of DNA in a human cell?

A

2 meters

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2
Q

What is the average diameter of a nucleus?

A

5-10 µm

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3
Q

Besides being packaged efficiently, what is another requirement for DNA packaging?

A

It needs to be dynamic for transcriptional regulation.

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4
Q

What is the diploid chromosome number in humans?

A

46 (23 pairs of chromosomes)

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5
Q

The four core histones are _________.

A

H2A, H2B, H3, and H4

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6
Q

What coincided with the emergence of core histones?

A

The emergence of eukaryotes

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7
Q

How is bacterial DNA packaged compared to eukaryotic DNA?

A

Bacterial DNA is loosely packaged by histone-like proteins, while eukaryotic DNA is tightly packaged by core histone proteins

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8
Q

Describe the ground state of gene regulation in bacteria versus eukaryotes.

A

Bacteria have a non-restrictive ground state, meaning genes are generally “on” unless repressed. Eukaryotes have a restrictive ground state, meaning genes are generally “off” unless activated.

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9
Q

Which histone is considered the “linker” histone?

A

H1

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10
Q

Which core histone exhibits the highest species conservation?

A

H4

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11
Q

What structural motif do histone dimers form through?

A

A “helical handshake”

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12
Q

Where is the histone fold located?

A

Within the globular domains of histones

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13
Q

The N-terminal tails of core histones are unstructured, _____ amino acids long, and rich in ________-charged _______ and _______.

A

20-30, positively, lysine and arginine

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14
Q

When does typical core histone synthesis occur?

A

During S phase

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15
Q

What type of proteins catalyzes core histone assembly?

A

Chromatin assembly factors (CAFs)

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16
Q

What is the function of the globular basic amino acids on the histone fold?

A

They bind tightly to the acidic DNA phosphodiester backbone

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17
Q

Are core histone N-terminal tails well-defined by X-ray crystallography?

A

No, suggesting flexibility and no major role within the core nucleosome itself.

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18
Q

Despite their lack of structure within the core nucleosome, what suggests the importance of core histone N-terminal tails?

A

They have highly conserved sequences in evolution.

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19
Q

How many base pairs of DNA are in a nucleosome core particle?

A

~147 bp

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20
Q

How many molecules of each core histone are in a nucleosome octamer?

A

2 molecules each of H2A, H2B, H3, and H4

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21
Q

Describe the winding of DNA around the core octamer in a nucleosome.

A

DNA is wound in 1.7 superhelical turns.

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22
Q

Describe the assembly of the histone octamer.

A

One tetramer of H3-H4 binds to DNA, followed by two H2A-H2B dimers.

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23
Q

What amino acids are abundant in core histone tails?

A

Lysine (K) and arginine (R)

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24
Q

What type of interactions are likely involved in contacts between adjacent nucleosomes?

A

Both histone-DNA and histone-histone interactions

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25
How do histone tails mediate inter-nucleosomal interactions?
Through charge-charge neutralization (acid-base electrostatic interactions)
26
What effect does H1 binding have on the nucleosome?
It induces a more compact and rigid conformation.
27
How does the H1 globular domain interact with DNA?
It interacts with core DNA on the dyad and with both DNA linkers.
28
Where does the H1 C-terminal domain primarily associate?
With a single DNA linker
29
What impact does H1 have on the nucleosome's symmetry?
It imparts a strong degree of asymmetry, likely influencing higher-order chromatin structure assembly.
30
What is the name of the structural fold found in the globular domain of linker histones?
Winged helix fold
31
How do both core and linker histones primarily interact with DNA?
Using positively charged arginine (R) and lysine (K) residues to interact with DNA backbone phosphates.
32
Describe the structure of linker histones.
They have a tripartite structure consisting of a globular domain and intrinsically disordered tails.
33
How does the ability to compact chromatin vary among H1 variants?
It varies; some have high, weak, or intermediate ability.
34
What are the two major types of chromatin?
Heterochromatin and euchromatin
35
Describe the condensation state of heterochromatin throughout the cell cycle.
Highly condensed
36
What are some characteristic features of heterochromatin?
Found in centromeres, telomeres, and some other chromosomal locations. Typically composed of highly repetitive DNA sequences (tandem repeats).
37
What typically happens to genes translocated into heterochromatic sequences?
They are transcriptionally inactivated.
38
What is the state of the inactive X chromosome in female somatic cells?
It is heterochromatic and highly condensed.
39
When does euchromatin become highly condensed?
Only at metaphase
40
Describe the condensation level of euchromatin during interphase.
Intermediate level of condensation
41
What is the transcriptional state of genes within euchromatin?
They can be transcriptionally active or inactive.
42
What are the components of chromatin?
DNA + core histones = nucleosomes + linker histone H1 (closes chromatin)
43
What cellular phases does interphase comprise?
G1, S, and G2 phases
44
What is the state of chromosomes during interphase?
Relatively decondensed
45
What phases are included in the M phase (mitosis)?
Prophase, metaphase, anaphase, telophase, and cytokinesis
46
When do chromosomes reach their maximum compaction?
At metaphase
47
What are the two important functional landmarks of chromosomes?
Centromere (links sister chromatids) and telomeres (chromosome ends)
48
Where are A-compartment domains positioned within chromosome territories?
Towards the nuclear interior
49
All somatic cell types within the body have the same set of ______ but exhibit unique patterns of chromatin and epigenetic states, which influence cell-type-specific gene expression profiles.
genes
50
___________ determine the timing, location, and level of promoter activation. They're crucial for cell-type specific gene regulation.
Transcription factors at the enhancer
51
The human haploid genome (a single set of chromosomes) comprises _______ bp
3E9
52
Length of DNA in an average human body (i.e., all cells counted) is estimated at ______ miles (6,000 times the distance of the moon from the Earth)
5E9
53
Bacteria DNA has ______ x compaction, while Eukaryotic DNA has __________ x compaction.
1,000; 10,000
54
Bacteria DNA is _________ (tightly/loosely) packed by histone-like proteins, while Eukaryotic DNA is __________ (tightly/loosely) packed by core histones.
loosely, tightly
55
There are ________ amino acids in H4.
102
56
There are _______ amino acids in H3.
135
57
There are _________ amino acids in H1.
220
58
H4 has an extremely high degree of conservation amongst species, while H1 has a _______ degree of conservation.
moderate
59
The ___________ in core histones (where the histone fold is situated) contain many buried hydrophobic amino acids, but also many positively charged residues at the surface that help dictate DNA binding geometry around the nucleosome.
globular domains
60
The process of octamer assembly is catalyzed by chaperone proteins called ____________. These are essential adjuncts to the process, since otherwise jumbled protein aggregates will form readily.
chromatin assembly factors (CAFs)
61
Typical core histone synthesis occurs during _______ phase, when DNA is being replicated.
S phase
62
The “globular” ______ (basic/acidic) amino acids (situated on the perimeter of the protein disc) are involved in binding tightly to the ______ (basic/acidic) DNA phosphodiester backbone
basic, acidic
63
A core nucleosome has approximately _____ bp of dsDNA wrapped around it.
147
64
Assembly of octamer proceeds by binding of one ________ (tetramer/dimer) of H3-H4 to DNA followed by two H2A-H2B _______ (tetramers/dimers).
tetramer, dimers
65
Core histone tails are extremely rich in ________ (amino acid) and _______ (amino acid), meaning they are highly _______ (negatively/positively) charged.
lysine, arginine, positively
66
True or False: In inter-nucleosomal interactions, histone-histone interactions are likely to be more important than histone-DNA interactions.
True
67
H1 binding induces the nucleosome to adopt a more _____________ conformation.
compact and rigid
68
The H1 globular domain interacts with ________ on the dyad and with both DNA linkers.
core DNA
69
The H1 C-terminal domain associates primarily with a single __________.
DNA linker
70
H1 imparts a strong degree of ___________ (symmetry/asymmetry) to the nucleosome, which is likely to influence the assembly and architecture of higher-order chromatin structures. The linker histone H1 also stabilizes a ______ nucleosome conformation.
asymmetry, compact
71
Linker histones has ____partite structure.
tri
72
True or False: Linker histone H1 molecules exist in many variant forms.
True
73
True or False: Genes within euchromatin can be transcriptionally active or inactive.
True
74
Interphase comprises the G1, S and G2 phases of the cell cycle – chromosomes are relatively ____________ (condensed/decondensed) during these stages
decondensed
75
Chromosomes contain two important functional landmarks – the ___________ that links sister chromatids, and _________ (chromosome ends).
centromere, telomeres
76
Gene expression and DNA replication occur in the cell cycle __________.
interphase
77
True or False: Individual chromosomes occupy distinct territories.
True
78
LADs stand for ______.
Lamina-associated domains
79
TADs stand for ________.
Topologically-associating domains
80
At smaller scales, chromatin is organized into insulated spatial neighborhoods referred to as _____ or loop domains.
TADs