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MolCell Unit 2 > Iwafuchi 1 > Flashcards

Iwafuchi 1 Flashcards

Flashcards for Iwafuchi Lecture 1

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
Q

How do histone tails mediate inter-nucleosomal interactions?

A

Through charge-charge neutralization (acid-base electrostatic interactions)

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26
Q

What effect does H1 binding have on the nucleosome?

A

It induces a more compact and rigid conformation.

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27
Q

How does the H1 globular domain interact with DNA?

A

It interacts with core DNA on the dyad and with both DNA linkers.

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28
Q

Where does the H1 C-terminal domain primarily associate?

A

With a single DNA linker

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29
Q

What impact does H1 have on the nucleosome’s symmetry?

A

It imparts a strong degree of asymmetry, likely influencing higher-order chromatin structure assembly.

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30
Q

What is the name of the structural fold found in the globular domain of linker histones?

A

Winged helix fold

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31
Q

How do both core and linker histones primarily interact with DNA?

A

Using positively charged arginine (R) and lysine (K) residues to interact with DNA backbone phosphates.

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32
Q

Describe the structure of linker histones.

A

They have a tripartite structure consisting of a globular domain and intrinsically disordered tails.

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33
Q

How does the ability to compact chromatin vary among H1 variants?

A

It varies; some have high, weak, or intermediate ability.

34
Q

What are the two major types of chromatin?

A

Heterochromatin and euchromatin

35
Q

Describe the condensation state of heterochromatin throughout the cell cycle.

A

Highly condensed

36
Q

What are some characteristic features of heterochromatin?

A

Found in centromeres, telomeres, and some other chromosomal locations. Typically composed of highly repetitive DNA sequences (tandem repeats).

37
Q

What typically happens to genes translocated into heterochromatic sequences?

A

They are transcriptionally inactivated.

38
Q

What is the state of the inactive X chromosome in female somatic cells?

A

It is heterochromatic and highly condensed.

39
Q

When does euchromatin become highly condensed?

A

Only at metaphase

40
Q

Describe the condensation level of euchromatin during interphase.

A

Intermediate level of condensation

41
Q

What is the transcriptional state of genes within euchromatin?

A

They can be transcriptionally active or inactive.

42
Q

What are the components of chromatin?

A

DNA + core histones = nucleosomes + linker histone H1 (closes chromatin)

43
Q

What cellular phases does interphase comprise?

A

G1, S, and G2 phases

44
Q

What is the state of chromosomes during interphase?

A

Relatively decondensed

45
Q

What phases are included in the M phase (mitosis)?

A

Prophase, metaphase, anaphase, telophase, and cytokinesis

46
Q

When do chromosomes reach their maximum compaction?

A

At metaphase

47
Q

What are the two important functional landmarks of chromosomes?

A

Centromere (links sister chromatids) and telomeres (chromosome ends)

48
Q

Where are A-compartment domains positioned within chromosome territories?

A

Towards the nuclear interior

49
Q

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.

A

genes

50
Q

___________ determine the timing, location, and level of
promoter activation. They’re crucial for cell-type specific gene regulation.

A

Transcription factors at the enhancer

51
Q

The human haploid genome (a single set of chromosomes) comprises _______ bp

A

3E9

52
Q

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)

A

5E9

53
Q

Bacteria DNA has ______ x compaction, while Eukaryotic DNA has __________ x compaction.

A

1,000; 10,000

54
Q

Bacteria DNA is _________ (tightly/loosely) packed by histone-like proteins, while Eukaryotic DNA is __________ (tightly/loosely) packed by core histones.

A

loosely, tightly

55
Q

There are ________ amino acids in H4.

A

102

56
Q

There are _______ amino acids in H3.

A

135

57
Q

There are _________ amino acids in H1.

A

220

58
Q

H4 has an extremely high degree of conservation amongst species, while H1 has a _______ degree of conservation.

A

moderate

59
Q

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.

A

globular domains

60
Q

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.

A

chromatin assembly factors (CAFs)

61
Q

Typical core histone synthesis occurs during _______ phase, when DNA is being replicated.

A

S phase

62
Q

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

A

basic, acidic

63
Q

A core nucleosome has approximately _____ bp of dsDNA wrapped around it.

A

147

64
Q

Assembly of octamer proceeds by binding of one ________ (tetramer/dimer) of H3-H4 to DNA followed by two H2A-H2B _______ (tetramers/dimers).

A

tetramer, dimers

65
Q

Core histone tails are extremely rich in ________ (amino acid) and _______ (amino acid), meaning they are highly _______ (negatively/positively) charged.

A

lysine, arginine, positively

66
Q

True or False: In inter-nucleosomal interactions, histone-histone interactions are likely to be more important than histone-DNA interactions.

A

True

67
Q

H1 binding induces the nucleosome to adopt
a more _____________ conformation.

A

compact and rigid

68
Q

The H1 globular domain interacts with ________ on the dyad and with both DNA linkers.

A

core DNA

69
Q

The H1 C-terminal domain associates primarily with a single __________.

A

DNA linker

70
Q

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.

A

asymmetry, compact

71
Q

Linker histones has ____partite structure.

A

tri

72
Q

True or False: Linker histone H1 molecules exist in many variant forms.

A

True

73
Q

True or False: Genes within euchromatin can be transcriptionally active or inactive.

A

True

74
Q

Interphase comprises the G1, S and G2 phases of the cell cycle – chromosomes are relatively
____________ (condensed/decondensed) during these stages

A

decondensed

75
Q

Chromosomes contain two important functional landmarks – the ___________ that links sister chromatids, and _________ (chromosome ends).

A

centromere, telomeres

76
Q

Gene expression and DNA replication occur in the cell cycle __________.

A

interphase

77
Q

True or False: Individual chromosomes occupy distinct territories.

A

True

78
Q

LADs stand for ______.

A

Lamina-associated domains

79
Q

TADs stand for ________.

A

Topologically-associating domains

80
Q

At smaller scales, chromatin is organized into insulated spatial
neighborhoods referred to as _____ or loop domains.

A

TADs

MolCell Unit 2 (13 decks)

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