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Molecular Biology > DNA, Chromosomes, and Genomes 2 (lecture 2) > Flashcards

DNA, Chromosomes, and Genomes 2 (lecture 2) Flashcards

1
Q

certain types of chromatin structure can be

A

inherited

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2
Q

A form of inheritance that is superimposed on the genetic inheritance based on DNA

A

Epigenetics

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3
Q

Epigenetics

A

A form of inheritance that is superimposed on the genetic inheritance based on DNA

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4
Q

Genomic ______ is the epigenetic phenomenon by which certain genes are expressed in a parent-of-origin-specific manner. if the allele inherited form the father is _____, it is thereby silenced, and only the allele from the mother is expressed

A

Imprinting, Imprinted

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5
Q

Examples of regulation of chromatin structure

A

-DNA methylation - Chromatin structure - Histone modification

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6
Q

examples of genomic imprinting

A

Prater Willie (on paternal portion of chromosome 15) Angelman syndrome (on maternal portion of chromosome 15)

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7
Q

Historically, _____ were thought to be just involved in packaging of DNA

A

Histones (note this is not the case now)

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8
Q

Mammalian chromatin contains equal mass of ___ and _____ proteins

A

histone and non-histone

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9
Q

histones are ____ conserved

A

highly

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10
Q

only 2 amino acid differences between mammalian and pea H4; therefore, any change must be

A

Deleterious

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11
Q

one form of chromatin (______) silences the genes it packages without regard to sequence and is directly inherited by daughter cells

A

heterochromatin

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12
Q

What challenges the view that histones are only involved in packaging of DNA

A

-Mammalian chromatin contains equal mass of histone and non histone proteins - Histones are highly conserved - One form of chromatin (heterochromatin) silences the genes it packages without regard to sequence and is directly inherited by daughter cells

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13
Q

Chromatin that is very condensed

A

Heterochromatin

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14
Q

other proteins binding to histones is suggestive of

A

function other than purely structural

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15
Q

Heterochromatin is hout to be

A

late replicating and genetically inactive

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16
Q

Heterochromatin is highly concentrated at ____ and ___

A

Centromeres and Telomeres

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17
Q

Heterochromatin contains very few _____; those that are present are

A

contains very few genes, those that are present are resistant to gene expression

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18
Q

Activity of a gene depends on position on chromosome

A

Position effect

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19
Q

Position effect

A

activity of a gene depends on position on chromosome

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20
Q

according to the position effect if a gene is relocated near heterochromatin then it will be

A

silenced

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21
Q

Less condensed chromatin is known as

A

Euchromatin

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22
Q

Heterochromatin is replicated

A

late in S phase

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23
Q

In a typical mammalian cell, more than ____% of the genome is packaged as heterochromatin

A

10%

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24
Q

When euchromatic regions are converted to heterochromatic state, their genes are

A

generally switched off

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25
Q

what is silencing of genes

A

inactivation.

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26
Q

Breakage events that bring heterochromatin near active genes tends to silence them

A

Position effect variegation

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27
Q

Position effect variegation

A

breakage events that bring heterochromatin near active genes tends to silence them

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28
Q

The zone of inactivation spreads a ______ distance in different cells

A

different

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29
Q

early in the developing embryo, ______ forms and spreads into neighboring _____ to different extents in different cells

A

Heterochromatin, Euchromatin

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30
Q

Amino acid side chains of Histones are subject to a variety of

A

covalent modifications

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31
Q

Amino acids side chains of histones are subject to a variety of covalent modifications occurring on the ____ of the histone as well as the ____

A

core, tail

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32
Q

What effect does the Acetylation of lysines on amino acid side chains of histones have

A

loosens chromatin structure

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33
Q

examples of covalent modifications of amino acid side chains of the four histones in the nucleosome core

A
  • Acetylation of lysines - mono-, di-, and trimethylation of lysines - phosphorylation of serines
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34
Q

Are the covalent modification of the amino acid side chains on histones reversible

A

yes. (one enzyme adds them and another removes them)

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35
Q

Function of Histone acetyl Transferases (HATs)

A

acetylation - add acetyl groups to specific lysines

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36
Q

Function of Histone deacetylase complexes (HDACs)

A

-Remove the acetyl groups for specific lysines

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37
Q

Function of histone methyl transferases

A

Methylation of lysines - add methyl groups to lysine side chains

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38
Q

Function of histone demethylases

A

remove methyl groups form the lysine side chains of histones

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39
Q

What recruits the enzymes to the specific sites on the chromatin for the covalent modification of histones

A

Transcription regulator proteins

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40
Q

function of methylation of the amino acid side chains of histones

A

leads to tightly packing chromatin and silencing genes

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41
Q

Amino acid side chains of histones are subject to a variety of covalent modifications one of them being the phosphorylation of ____

A

serines

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42
Q

All the covalent modifications of amino acid side chains of histones are reversible but can _______ after _____ have disappeared. Thereby providing the cell with a memory of

A

persist long after regualtory proteins have disappeared, thereby providing the cell with a memory of its developmental history

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43
Q

At some positions lysine can be modified either by ___ or by ____, but not both

A

methylation, acetylation

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44
Q

Why does acetylation of lysines on the N-terminal tails loosen chromatin strucuture

A

because adding an acetyl group to lysine removes its positive charge, thereby reducing the affinity of the tails for adjacent nucleosomes.

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45
Q

important consequences for the types of proteins the modified DNA attracts: this determines

A

this determines how/when/if gene expression takes place

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46
Q

Variants exist for each of the core histones except for

A

H4

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47
Q

Variant histone proteins are present in much _____ amounts than core histones and are ______ _____ conserved

A

much smaller amounts than core histones and are less well-conserved

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48
Q

Major histones are synthesized during ____ and are assembled into ____ on daughter DNA helices just behind _____

A

Are synthesized during S-phase and assembled into nucleosomes on daughter DNA helices just behind the replication fork

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49
Q

Variant histones (most anyway) are synthesized during ______ and inserted into _________. This requires _____ catalyzed by ______

A

are synthesized during interphase and inserted into already-formed chromatin. This requires histone exchange process catalyzed by ATP-dependent chromatin remodeling complex

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50
Q

ATP-dependent chromatin remodeling complexes contain subunits that cause them to bind both to specific sits on _____ and to _____ that carry a particular variant

A

chromatin and to histone chaperones

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51
Q

due to the ATP-dependent chromatin remodeling complex each histone variant is inserted into chromatin in a

A

highly selective manner

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52
Q

CENP-A is a variant of histone

A

H3

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53
Q

What is the special function(s) of H3.3

A

Transcriptional activation

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54
Q

What is the special function(s) of CENP-A (a variant of H3)

A

Centromere function and kinetochore assembly

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55
Q

What is the special function(s) of H2AX (variant of H2A)

A

DNA repair and recombination

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56
Q

What is the special function(s) of H2AZ (variant of H2A)

A

Gene expression and chromsome segregation

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57
Q

What is the special function(s) of macroH2A (variant of H2A)

A

Transcriptional repression and X-chromosome inactivation

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58
Q

H2AX is a variant of histone

A

H2A

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59
Q

H2AZ is a variant of histone

A

H2A

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60
Q

MacroH2A is a variant of histone

A

H2A

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61
Q

Thousands of combinations of modifications (methylation, acetylation,phosphorylation) may exist; further diversity is created by

A

variant histones

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62
Q

Histone code

A

-One type of marking signals that a stretch of chromatin has been newly replicated, another signals that the DNA in that chromatin has been damaged and needs repair, while others signal when and how gene expression should take place

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63
Q

a _____ allows particular combinations of markings on chromatin to attract additional proteins, so as to execute an appropriate biological function at the right time

A

reader complex

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64
Q

the histone code has a specific meaning for the cell, determining

A

how/when DNA is packaged in nucleosome

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65
Q

The histone code is read by the _______, which involves joint recognition of histone tail and covalent modifications

A

code reader complex

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66
Q

______ involves joint recognition of histone tail and covalent modifications

A

code reader complex

67
Q

Histone code can change as

A

the cell needs change

68
Q

The code-reader complex binds and attracts other components thus making a protein complex with catalytic activities and additional binding sites which attachment to other components in nucleus leads to

A

gene expression gene silencing or other biological function

69
Q

Reading histone code involves joint recognition of marks at other sites on _____ along with ____ recognition

A

nucleosome along with tail recognition

70
Q

A large protein complex that contains a series of protein modules each of which recognizes a specific histone mark

A

Reader complex

71
Q

The reader complex will bind tightly only to a region of chromatin that contains

A

several of the different histone marks that it recognizes, therefore only a specific combination of marks will cause the complex to bind to chromatin and attract the additional protein complexes needed to catalyze biological function

72
Q

The trimethylation of lysine 9 on the histone H3 N-terminal tail attracts the

A

heterochromatin-specific protein HP1, which induces a spreading wave of further lysine 9 trimethylation followed by further HP1 binding

73
Q

Trimethylation of lysine 9 one the histone H-3 N-terminal tail has what meaning

A

heterochromatin formation gene silencing

74
Q

The trimethylation of lysine 4 with acetylation of lysine-9 on the histone H3 N-terminal tail has what meaning

A

Gene expression

75
Q

The trimethylation of lysine-27 on the histone H3 N-terminal tail has what meaning

A

Silencing of Hox genes X chromosome inactivation

76
Q

The phosphorylation of serine-10 with the acetylation of lysine-14 on the histone H3 N-terminal tail has what meaning

A

gene expression

77
Q

After modifying enzyme marks one or few neighboring nucleosomes, _____ reactions can ensue

A

chain reactions

78
Q

______ enzymes spread the mark over the chromosome

A

Code reader-writer

79
Q

_____ is an enzyme that creates a specific modification on one or more of the four nucleosomal histones

A

Writer protein

80
Q

in order for the reader-writer complex to spread chromatin changes along a chromosome the reader must

A

recognize the same histone modification mark that the writer produces; its binding to that mark can be shown to activate the writer (note that an ATP-dependent chromatin remodeling complex is required to reposition the modified nucleosomes)

81
Q

explain the reader-writer complex

A
  • writer enzymes that add or remove modifications to histones in nucleosomes are initially brought to a particular region of chromatin by one of the sequence-specific DNA-binding proteins - after a writer enzyme makes its mark on one or a few neighboring nucleosomes, events that resemble a chain reaction can ensue. - a writer enzyme now works in concert with a reader protein located in the same protein complex. The reader protein contains a module that recognizes the mark and binds tightly to the newly modified nucleosome activating an attached enzyme and positioning it near an adjacent nucleosome - an ATP-dependent chromatin remodeling protein work in concert to either decidedness or condense long stretches of chromatin as the reader moves progressively along the nucleosome-packaged DNA - through many such reader-writer cycles, the reader protein can carry the writer enzyme along the DNA thus spreading the mark in a hand-over hand manner along the chromosome
82
Q

what are some barrier sequences that halt the spread of chromatin modifications

A

-Several mechanisms - Physical barriers -Enzymatic barriers

83
Q

Give an example(s) of an enzymatic barrier that halts the spread of chromatin modification

A
  • -HS4 region -
    • The clustering of histones acetylene leads to loose chromatin
    • Protects the Beta global locus from silencing
    • Contains a cluster of histone acetylene binding sites
  • By recruiting a group of highly active histone-modifying enzymes, barriers can erase the histone marks that are required for heterochromatin to spread
    • for example, a potent acetylation of lysine 9 on histone H3 will compete with lysine 9 methylation, thereby preventing the binding of the HP1 protein needed to form a major form of heterochromatin
84
Q

what happens if the HS4 sequence in cells destined to be re blood cells is deleted

A

-HS4 normally separates the active chromatin domain that contains the human beta-globin locus from an adjacent region of silenced, condensed chromatin. - if the sequence is deleted, the beta-globin locus is invaded by condensed chromatin - this chromatin silences the genes it covers, and spreads to a different extend in different cells, thus causing position effect variegation - the global genes are poorly expressed, and the individuals who carry such a deletion have a severe form of anemia

85
Q

HS4 acts as an enzymatic barrier because it contains a cluster of binding sites for histone acetylase enzymes. How does this act as a barrier

A
  • Since the acetylation of a lysine side chain is incompatible with the methylation of the same side chain, and specific lysine methylations are required to spread heterochromatin, histone acetylates are logical candidates for the formation of DNA barriers to spreading of heterochromatin
86
Q

give two examples of physical barriers to block the spread of reader-writer complexes and thereby separate neighboring chromatin domains

A
  • Tethering of a region of chromatin to a large fixed site, such as the nuclear pore complex, can form a barrier that stops the spread of heterochromatin - The tight binding of barrier proteins to a group of nucleosomes can make this chromatin resistant to heterochromatin spreading
87
Q

Centromeric heterochromatin contains centromere-specific H3 histone, _____, an other proteins that pack the nucleosomes into dense arrangements to form the ______, a structure required for attachment of the mitotic spindle

A

CENP-A, Kinetochore

88
Q

The centromere sequences in humans consist of short repetitive DNA sequences called

A

alpha satellite DNA

89
Q

new centromeres (neocentromeres) can form spontaneously on

A

fragmented chromosomes, some of which lack alpha satellite DNA

90
Q

alpha satellite DNA are also found at non-centromeric positions on chromosomes, indicating

A

that they are not sufficient to direct centromere formation

91
Q

Centromeres in complex organisms are defend by _____ , rather than by _____

A

defined by an assembly of proteins, rather than by a specific DNA sequence

92
Q

De novo centromere formation requires a _____ event on _______

A

requires a seeding event on alpha satellite DNA

93
Q

_____ are directly inherited by the daughter strands at the replication fork

A

H3-H4 tetramers

94
Q

Once the initial seeding event on the alpha satellite DNA has occurred

A

it will be directly inherited in each round of replication

95
Q

____ chromosomes form amphibian oocytes are the largest chromosomes known

A

Lampbrush

96
Q

Lampbrush chromosomes from amphibian oocytes can be

A

visualized by light microscopy

97
Q

How the packaging of DNA in chromatin can be inherited following chromosome replication

A

some of the specialized chromatin components are distributed to each sister chromosome after DNA duplication, along with the specially marked nucleosomes that they bind. After DNA replication, the inherited nucleosomes that are specially modified, acting in concert with the inherited chromatin components, change the pattern of histone modification on the newly formed nucleosomes nearby. This creates new binding sites for the same chromatin components, which then assemble to complete the structure. - A cooperative recruitment of proteins, along with the action of reader-writer complexes, can thus not only account for the spreading of specific forms of chromatin in space along the chromosome, but also for its propagation across cell generations- form parent cell to daughter cells

98
Q

The lamp brush chromosomes form amphibian oocytes are visualized in a series of

A

large chromatin loops emanating form the linear chromosome axis

99
Q

in the lampbrush chromosomes the large loops contain ____ that remains extending in the same manner as the oocyte grows

A

DNA Sequence

100
Q

Each chromosome occupies ________ in the nucleus

A

its own area

101
Q

Heterochromatin preferentially associates with the

A

nuclear lamina

102
Q

Gene-rich regions of chromatin are

A

dispersed throughout the nucleus

103
Q

Each of the ___ interphase chromosomes in a human cell tends to occupy its own discrete territory within the nucleus

A

46

104
Q

position of a gene in the interior of the nucleus _____ when it becomes highly expressed

A

changes

105
Q

most chromsome puffs arise from

A

the decondensation of a single chromosome band during gene transcription

106
Q

Chromosome puffs

A

Decondensation of chromatin during gene transcription

107
Q

Actively transcribed genes extend

A

out of its area on an extended chromosome loop

108
Q

The interior of the nucleus is very

A

heterogeneous

109
Q

Distinct biochemical environment of the nucleus have high local concentrations of ___ and _____

A

enzymes and molecules for specific processes such as DNA repair “foci” and RNA synthesis

110
Q

Different _____ of the nucleus have effects on gene expression

A

neighborhoods

111
Q

Mitotic chromosomes are ____ condensed

A

highly

112
Q

final level in chromosome packaging

A

Mitotic Chromosomes

113
Q

two daughter DNA molecules replicated in interphase are separately folded to produce _________

A

two sister chromatids

114
Q

Chromatids are held together at their

A

centromeres

115
Q

how many nanometers wide is a short region of the DNA double helix

A

about 2 nanometers

116
Q

how many nanometers wide is a beads on a string form of chromatin

A

about 11 nanometers wide

117
Q

How many nanometers is chromatin fiber of packed nucleosomes

A

about 30 nanometers

118
Q

who many nanometers is a section of chromosome in extended form

A

about 300 nanometers wide

119
Q

How many nanometers wide is a condensed section of chromosome

A

about 700 nanometers wide

120
Q

how many nanometers is the entire mitotic chromosome

A

about 1400 nanometers wide

121
Q

the net result of mitotic chromosomes packaging is that each DNA molecule has been packaged into a mitotic chromosome that is _______ fold shorter than its extended length

A

10,000-fold

122
Q

what is the purpose of condensation of mitotic chromosomes

A

-Disentanglement of sister chromatids to allow separation for cell division - Protection of fragile DNA molecule as separation occurs

123
Q

Compaction of DNA is aided by proteins called

A

condensins

124
Q

Condensins use _____ to coil the DNA molecules into chromatids

A

ATP hydrolysis

125
Q

condensins are a major structural component of the core of every

A

metaphase chromosome

126
Q

Cells depleted of condensins have

A

abnormal condensation

127
Q

is the exact mechanism of condensation by condensins known

A

No

128
Q

Genes that are similar in both sequence and function due to common ancestry

A

Homologues

129
Q

Human homologues exist in ____,____,_____ and ____

A

yeast, worms, fruit flies and bacteria

130
Q

Recognition of ______ is a major clue to gene and protein function

A

sequence similarity

131
Q

_____ are more tightly conserved than genome structure

A

gene sequences

132
Q

Size of genome, number of genes, size of introns, abundance of repetitive sequences can be

A

quite different

133
Q

number of genes only roughly correlated with ____ complexity of organism

A

phenotypic

134
Q

Phenotypic complexity of an organism arises form

A

duplication and expansion of related gene families

135
Q

how do genomic changes occur

A

-as mistakes in DNA replication and repair - movement of transposable elements also play a role

136
Q

Mistakes in DNA replication and repair are rare and only _______ nucleotide pairs is randomly changed in the germ line every million years

A

1/1000

137
Q

what are the range of genomic changes that can occur

A

-Base pair substitutions - Large Scale rearrangements - Duplications - Deletions - Inversions - Translocations

138
Q

_____ shows differences between humans and apes

A

phylogenetic tree

139
Q

What are some reasons for genome sequence conservations

A

-not having much time for mutations to occur since lineages separated - purifying selection

140
Q

what is purifying selection

A

-Elimination of mutations that interferes with important genetic functions

141
Q

In comparative genomics we can reconstruct genome evolution by comparing genomes of

A

contemporary organisms

142
Q

how many million of years ago did humans diverge from chimpanzees

A

5 million years

143
Q

what percent of nucleotide substitution is different between humans and chimpanzees

A

0.5 percent

144
Q

the puffer fish genome is ___ billion base pairs compared to ____ billion in other fish

A

0.4 billion base pairs compared to 1.0 billion in other fish

145
Q

Can genome size vary considerably

A

yes

146
Q

why is the puffer fish genome so small

A

due to small introns - thus lacks repetitive DNA

147
Q

in the genome of the puffer fish and humans the intron position of the ____ gene is conserved

A

huntingtin gene

148
Q

Sequence comparisons can provide insight into ___ or ____

A

purpose or function

149
Q

___% of human genome is conserved, but only ____% codes for proteins

A

5% of human genome is conserved, but only 1.5% codes for proteins

150
Q

the 3.5% of the human genome that is conserved and does not code for proteins must have an important function such as

A

-RNA molecules - Regulatory regions

151
Q

What are Pseudogenes

A

a duplicated gene that has become irreversibly inactivated by multiple mutations

152
Q

explain duplication and divergence in gene duplication? give an example

A

both copies remain functional while diverging in sequence and pattern of expression - ex. Globin gene family derives form common ancestral gene

153
Q

in gene duplication with little selective pressure to maintain mutation-free what occurs

A

many duplication events are likely to be followed by loss-of-function mutations in one or the other gene. This cycle would functionally restore the one gene state that preceded the duplication. Indeed, there are many examples in contemporary genomes where one copy of a duplicated gene can be seen to have become irreversibly inactivated by multiple mutations. Over time, the sequence similarity between such a pseudogene and the functional gene whose duplication produced it would be expected to be eroded by the accumulation of many mutations in the pseudogene - the homologous relationship eventually becoming undetectable

154
Q

Explain the evolution of the globin gene family

A

duplication and mutation gave rise to Beta and alpha genes - translocation moved alpha to separate chromosome (chromosome 16) - further duplication and mutation resulted in more specialized beta molecules (both on chromosome 11)

155
Q

Human DNA sequences vary ____% from one another

A

0.1%

156
Q

human and chimp DNA sequences differ ___% from one another

A

1%

157
Q

the majority of DNA mutations are neither

A

harmful or beneficial

158
Q

______ mutations can become fixed in a population

A

neutral

159
Q

What are the intraspecies variations that have been most extensively characterized

A

single-nucleotide polymorphisms (SNPs)

160
Q

simply points in the genome sequence where one large fraction of the human population has one nucleotide, while another substantial fraction has another

A

Single-nucleotide polymorphisms (SNPs)

161
Q

presence of many duplications and deletions of large blocks of DNA

A

Copy Number variations (CNVs)

162
Q

CNVS at some blocks are common and other rare; but the _____ of most is unknown

A

significance

163
Q

SNPs (Singl-nucleotide polymorphisms) occur at a high rate of about

A

1% or more

Molecular Biology (14 decks)

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