DNA, Chromosomes, and Genomes 2 (lecture 2) Flashcards
1
Q
certain types of chromatin structure can be
A
inherited
2
Q
A form of inheritance that is superimposed on the genetic inheritance based on DNA
A
Epigenetics
3
Q
Epigenetics
A
A form of inheritance that is superimposed on the genetic inheritance based on DNA
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
5
Q
Examples of regulation of chromatin structure
A
-DNA methylation - Chromatin structure - Histone modification
6
Q
examples of genomic imprinting
A
Prater Willie (on paternal portion of chromosome 15) Angelman syndrome (on maternal portion of chromosome 15)
7
Q
Historically, _____ were thought to be just involved in packaging of DNA
A
Histones (note this is not the case now)
8
Q
Mammalian chromatin contains equal mass of ___ and _____ proteins
A
histone and non-histone
9
Q
histones are ____ conserved
A
highly
10
Q
only 2 amino acid differences between mammalian and pea H4; therefore, any change must be
A
Deleterious
11
Q
one form of chromatin (______) silences the genes it packages without regard to sequence and is directly inherited by daughter cells
A
heterochromatin
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
13
Q
Chromatin that is very condensed
A
Heterochromatin
14
Q
other proteins binding to histones is suggestive of
A
function other than purely structural
15
Q
Heterochromatin is hout to be
A
late replicating and genetically inactive
16
Q
Heterochromatin is highly concentrated at ____ and ___
A
Centromeres and Telomeres
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
18
Q
Activity of a gene depends on position on chromosome
A
Position effect
19
Q
Position effect
A
activity of a gene depends on position on chromosome
20
Q
according to the position effect if a gene is relocated near heterochromatin then it will be
A
silenced
21
Q
Less condensed chromatin is known as
A
Euchromatin
22
Q
Heterochromatin is replicated
A
late in S phase
23
Q
In a typical mammalian cell, more than ____% of the genome is packaged as heterochromatin
A
10%
24
Q
When euchromatic regions are converted to heterochromatic state, their genes are
A
generally switched off
25
what is silencing of genes
inactivation.
26
Breakage events that bring heterochromatin near active genes tends to silence them
Position effect variegation
27
Position effect variegation
breakage events that bring heterochromatin near active genes tends to silence them
28
The zone of inactivation spreads a ______ distance in different cells
different
29
early in the developing embryo, ______ forms and spreads into neighboring _____ to different extents in different cells
Heterochromatin, Euchromatin
30
Amino acid side chains of Histones are subject to a variety of
covalent modifications
31
Amino acids side chains of histones are subject to a variety of covalent modifications occurring on the ____ of the histone as well as the \_\_\_\_
core, tail
32
What effect does the Acetylation of lysines on amino acid side chains of histones have
loosens chromatin structure
33
examples of covalent modifications of amino acid side chains of the four histones in the nucleosome core
- Acetylation of lysines - mono-, di-, and trimethylation of lysines - phosphorylation of serines
34
Are the covalent modification of the amino acid side chains on histones reversible
yes. (one enzyme adds them and another removes them)
35
Function of Histone acetyl Transferases (HATs)
acetylation - add acetyl groups to specific lysines
36
Function of Histone deacetylase complexes (HDACs)
-Remove the acetyl groups for specific lysines
37
Function of histone methyl transferases
Methylation of lysines - add methyl groups to lysine side chains
38
Function of histone demethylases
remove methyl groups form the lysine side chains of histones
39
What recruits the enzymes to the specific sites on the chromatin for the covalent modification of histones
Transcription regulator proteins
40
function of methylation of the amino acid side chains of histones
leads to tightly packing chromatin and silencing genes
41
Amino acid side chains of histones are subject to a variety of covalent modifications one of them being the phosphorylation of \_\_\_\_
serines
42
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
persist long after regualtory proteins have disappeared, thereby providing the cell with a memory of its developmental history
43
At some positions lysine can be modified either by ___ or by \_\_\_\_, but not both
methylation, acetylation
44
Why does acetylation of lysines on the N-terminal tails loosen chromatin strucuture
because adding an acetyl group to lysine removes its positive charge, thereby reducing the affinity of the tails for adjacent nucleosomes.
45
important consequences for the types of proteins the modified DNA attracts: this determines
this determines how/when/if gene expression takes place
46
Variants exist for each of the core histones except for
H4
47
Variant histone proteins are present in much _____ amounts than core histones and are ______ \_\_\_\_\_ conserved
much smaller amounts than core histones and are less well-conserved
48
Major histones are synthesized during ____ and are assembled into ____ on daughter DNA helices just behind \_\_\_\_\_
Are synthesized during S-phase and assembled into nucleosomes on daughter DNA helices just behind the replication fork
49
Variant histones (most anyway) are synthesized during ______ and inserted into \_\_\_\_\_\_\_\_\_. This requires _____ catalyzed by \_\_\_\_\_\_
are synthesized during interphase and inserted into already-formed chromatin. This requires histone exchange process catalyzed by ATP-dependent chromatin remodeling complex
50
ATP-dependent chromatin remodeling complexes contain subunits that cause them to bind both to specific sits on _____ and to _____ that carry a particular variant
chromatin and to histone chaperones
51
due to the ATP-dependent chromatin remodeling complex each histone variant is inserted into chromatin in a
highly selective manner
52
CENP-A is a variant of histone
H3
53
What is the special function(s) of H3.3
Transcriptional activation
54
What is the special function(s) of CENP-A (a variant of H3)
Centromere function and kinetochore assembly
55
What is the special function(s) of H2AX (variant of H2A)
DNA repair and recombination
56
What is the special function(s) of H2AZ (variant of H2A)
Gene expression and chromsome segregation
57
What is the special function(s) of macroH2A (variant of H2A)
Transcriptional repression and X-chromosome inactivation
58
H2AX is a variant of histone
H2A
59
H2AZ is a variant of histone
H2A
60
MacroH2A is a variant of histone
H2A
61
Thousands of combinations of modifications (methylation, acetylation,phosphorylation) may exist; further diversity is created by
variant histones
62
Histone code
-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
63
a _____ allows particular combinations of markings on chromatin to attract additional proteins, so as to execute an appropriate biological function at the right time
reader complex
64
the histone code has a specific meaning for the cell, determining
how/when DNA is packaged in nucleosome
65
The histone code is read by the \_\_\_\_\_\_\_, which involves joint recognition of histone tail and covalent modifications
code reader complex
66
\_\_\_\_\_\_ involves joint recognition of histone tail and covalent modifications
code reader complex
67
Histone code can change as
the cell needs change
68
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
gene expression gene silencing or other biological function
69
Reading histone code involves joint recognition of marks at other sites on _____ along with ____ recognition
nucleosome along with tail recognition
70
A large protein complex that contains a series of protein modules each of which recognizes a specific histone mark
Reader complex
71
The reader complex will bind tightly only to a region of chromatin that contains
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
The trimethylation of lysine 9 on the histone H3 N-terminal tail attracts the
heterochromatin-specific protein HP1, which induces a spreading wave of further lysine 9 trimethylation followed by further HP1 binding
73
Trimethylation of lysine 9 one the histone H-3 N-terminal tail has what meaning
heterochromatin formation gene silencing
74
The trimethylation of lysine 4 with acetylation of lysine-9 on the histone H3 N-terminal tail has what meaning
Gene expression
75
The trimethylation of lysine-27 on the histone H3 N-terminal tail has what meaning
Silencing of Hox genes X chromosome inactivation
76
The phosphorylation of serine-10 with the acetylation of lysine-14 on the histone H3 N-terminal tail has what meaning
gene expression
77
After modifying enzyme marks one or few neighboring nucleosomes, _____ reactions can ensue
chain reactions
78
\_\_\_\_\_\_ enzymes spread the mark over the chromosome
Code reader-writer
79
\_\_\_\_\_ is an enzyme that creates a specific modification on one or more of the four nucleosomal histones
Writer protein
80
in order for the reader-writer complex to spread chromatin changes along a chromosome the reader must
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
explain the reader-writer complex
- 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
what are some barrier sequences that halt the spread of chromatin modifications
-Several mechanisms - Physical barriers -Enzymatic barriers
83
Give an example(s) of an enzymatic barrier that halts the spread of chromatin modification
* -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
what happens if the HS4 sequence in cells destined to be re blood cells is deleted
-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
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
- 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
give two examples of physical barriers to block the spread of reader-writer complexes and thereby separate neighboring chromatin domains
- 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
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
CENP-A, Kinetochore
88
The centromere sequences in humans consist of short repetitive DNA sequences called
alpha satellite DNA
89
new centromeres (neocentromeres) can form spontaneously on
fragmented chromosomes, some of which lack alpha satellite DNA
90
alpha satellite DNA are also found at non-centromeric positions on chromosomes, indicating
that they are not sufficient to direct centromere formation
91
Centromeres in complex organisms are defend by _____ , rather than by \_\_\_\_\_
defined by an assembly of proteins, rather than by a specific DNA sequence
92
De novo centromere formation requires a _____ event on \_\_\_\_\_\_\_
requires a seeding event on alpha satellite DNA
93
\_\_\_\_\_ are directly inherited by the daughter strands at the replication fork
H3-H4 tetramers
94
Once the initial seeding event on the alpha satellite DNA has occurred
it will be directly inherited in each round of replication
95
\_\_\_\_ chromosomes form amphibian oocytes are the largest chromosomes known
Lampbrush
96
Lampbrush chromosomes from amphibian oocytes can be
visualized by light microscopy
97
How the packaging of DNA in chromatin can be inherited following chromosome replication
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
The lamp brush chromosomes form amphibian oocytes are visualized in a series of
large chromatin loops emanating form the linear chromosome axis
99
in the lampbrush chromosomes the large loops contain ____ that remains extending in the same manner as the oocyte grows
DNA Sequence
100
Each chromosome occupies ________ in the nucleus
its own area
101
Heterochromatin preferentially associates with the
nuclear lamina
102
Gene-rich regions of chromatin are
dispersed throughout the nucleus
103
Each of the ___ interphase chromosomes in a human cell tends to occupy its own discrete territory within the nucleus
46
104
position of a gene in the interior of the nucleus _____ when it becomes highly expressed
changes
105
most chromsome puffs arise from
the decondensation of a single chromosome band during gene transcription
106
Chromosome puffs
Decondensation of chromatin during gene transcription
107
Actively transcribed genes extend
out of its area on an extended chromosome loop
108
The interior of the nucleus is very
heterogeneous
109
Distinct biochemical environment of the nucleus have high local concentrations of ___ and \_\_\_\_\_
enzymes and molecules for specific processes such as DNA repair "foci" and RNA synthesis
110
Different _____ of the nucleus have effects on gene expression
neighborhoods
111
Mitotic chromosomes are ____ condensed
highly
112
final level in chromosome packaging
Mitotic Chromosomes
113
two daughter DNA molecules replicated in interphase are separately folded to produce \_\_\_\_\_\_\_\_\_
two sister chromatids
114
Chromatids are held together at their
centromeres
115
how many nanometers wide is a short region of the DNA double helix
about 2 nanometers
116
how many nanometers wide is a beads on a string form of chromatin
about 11 nanometers wide
117
How many nanometers is chromatin fiber of packed nucleosomes
about 30 nanometers
118
who many nanometers is a section of chromosome in extended form
about 300 nanometers wide
119
How many nanometers wide is a condensed section of chromosome
about 700 nanometers wide
120
how many nanometers is the entire mitotic chromosome
about 1400 nanometers wide
121
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
10,000-fold
122
what is the purpose of condensation of mitotic chromosomes
-Disentanglement of sister chromatids to allow separation for cell division - Protection of fragile DNA molecule as separation occurs
123
Compaction of DNA is aided by proteins called
condensins
124
Condensins use _____ to coil the DNA molecules into chromatids
ATP hydrolysis
125
condensins are a major structural component of the core of every
metaphase chromosome
126
Cells depleted of condensins have
abnormal condensation
127
is the exact mechanism of condensation by condensins known
No
128
Genes that are similar in both sequence and function due to common ancestry
Homologues
129
Human homologues exist in \_\_\_\_,\_\_\_\_,\_\_\_\_\_ and \_\_\_\_
yeast, worms, fruit flies and bacteria
130
Recognition of ______ is a major clue to gene and protein function
sequence similarity
131
\_\_\_\_\_ are more tightly conserved than genome structure
gene sequences
132
Size of genome, number of genes, size of introns, abundance of repetitive sequences can be
quite different
133
number of genes only roughly correlated with ____ complexity of organism
phenotypic
134
Phenotypic complexity of an organism arises form
duplication and expansion of related gene families
135
how do genomic changes occur
-as mistakes in DNA replication and repair - movement of transposable elements also play a role
136
Mistakes in DNA replication and repair are rare and only _______ nucleotide pairs is randomly changed in the germ line every million years
1/1000
137
what are the range of genomic changes that can occur
-Base pair substitutions - Large Scale rearrangements - Duplications - Deletions - Inversions - Translocations
138
\_\_\_\_\_ shows differences between humans and apes
phylogenetic tree
139
What are some reasons for genome sequence conservations
-not having much time for mutations to occur since lineages separated - purifying selection
140
what is purifying selection
-Elimination of mutations that interferes with important genetic functions
141
In comparative genomics we can reconstruct genome evolution by comparing genomes of
contemporary organisms
142
how many million of years ago did humans diverge from chimpanzees
5 million years
143
what percent of nucleotide substitution is different between humans and chimpanzees
0.5 percent
144
the puffer fish genome is ___ billion base pairs compared to ____ billion in other fish
0.4 billion base pairs compared to 1.0 billion in other fish
145
Can genome size vary considerably
yes
146
why is the puffer fish genome so small
due to small introns - thus lacks repetitive DNA
147
in the genome of the puffer fish and humans the intron position of the ____ gene is conserved
huntingtin gene
148
Sequence comparisons can provide insight into ___ or \_\_\_\_
purpose or function
149
\_\_\_% of human genome is conserved, but only \_\_\_\_% codes for proteins
5% of human genome is conserved, but only 1.5% codes for proteins
150
the 3.5% of the human genome that is conserved and does not code for proteins must have an important function such as
-RNA molecules - Regulatory regions
151
What are Pseudogenes
a duplicated gene that has become irreversibly inactivated by multiple mutations
152
explain duplication and divergence in gene duplication? give an example
both copies remain functional while diverging in sequence and pattern of expression - ex. Globin gene family derives form common ancestral gene
153
in gene duplication with little selective pressure to maintain mutation-free what occurs
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
Explain the evolution of the globin gene family
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
Human DNA sequences vary \_\_\_\_% from one another
0.1%
156
human and chimp DNA sequences differ \_\_\_% from one another
1%
157
the majority of DNA mutations are neither
harmful or beneficial
158
\_\_\_\_\_\_ mutations can become fixed in a population
neutral
159
What are the intraspecies variations that have been most extensively characterized
single-nucleotide polymorphisms (SNPs)
160
simply points in the genome sequence where one large fraction of the human population has one nucleotide, while another substantial fraction has another
Single-nucleotide polymorphisms (SNPs)
161
presence of many duplications and deletions of large blocks of DNA
Copy Number variations (CNVs)
162
CNVS at some blocks are common and other rare; but the _____ of most is unknown
significance
163
SNPs (Singl-nucleotide polymorphisms) occur at a high rate of about
1% or more
