Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

BCHM218 > Module 3 Sections 6-8 > Flashcards

Module 3 Sections 6-8 Flashcards

genome structure and formatting, chromosome organization and packaging, chromatin remodeling and histone modifications

1
Q

genomes

A

complete set of genetic material encoded in a cell or virus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what do genomes contain

A

1 set of autosomes and 2 sex chromosomes

contains both coding and non-coding information, both functional and non-functional components of DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

prokaryotic genomes

A

mostly functional DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

eukaryotic genomes

A

mostly non-functional DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

functional DNA in the genome

A

highly conserved because it improves an organism’s fitness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

non-functional DNA in the genome

A

has no known biological contributions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

coding DNA (from functional DNA)

A

codes for a specific protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

non coding DNA (from functional DNA)

A

does not code for a protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

the human genome has:

A

3 billion nucleotide base pairs

23 pairs of chromosomes (22 autosomes and 2 sex chromosomes (1 pair))

estimated 20,000-25,000 genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

genomic complexity

A

analysis and comparison of different genomes of the 3 major domains of life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

3 major domains of life

A
  1. bacteria
  2. archaea
  3. eukaryotes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

bacteria domain

A

Small prokaryotic microorganisms

Have a plasma membrane but no internal organelles or nucleus

Have a genome consisting of a single, circular DNA molecule that is several million base pairs long

First genome sequenced was the bacterium Haemophilus influenzae

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

archaea domain

A

Like bacteria, unicellular organisms with no internal organelles or nucleus

Similar appearance to bacteria, but are more closely related to eukaryotes with respect to some genes and metabolic pathways

Have many species that thrive in extreme environments of high ionic strength, high temperature, or low pH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

eukaryote domain

A

Unicellular or multicellular organisms with cells having a membrane-bounded nucleus, multiple chromosomes and internal organelles

Genomes larger than bacteria and archaea with billions of nucleotides

Orthologs (genes of different species that evolved from a common ancestor)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

the human chromosome

A

arranged into 46 chromosomes

ranging from 50-250 million base pairs of DNA

22 homologous pairs of autosomes and 2 sex chromosomes or 1 pair (females have 2 X, males have 1 X and 1 Y)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

human chromosome structure

A

P-arm (shorter)
Q-arm (longer)
Centromere

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

human chromosome banding pattern

A

Unique band pattern when stained with a dye called Giemsa

Dark bands are heterochromatin, areas which stain heavily. It is the condensed portion of chromosomes that are not transcriptionally active

Lighter bands are euchromatin, which stains poorly or not at all. These regions are the genes that are being actively expressed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

humans vs primates similarities

A

shared a common ancestor around 7 million years ago

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

humans vs primates differences

A

apes = 24 pairs of chromosomes
humans = 23 pairs

humans have one chromosome 2 (result of end-to-end fusion of 2 ape chromosomes)
primates have two chromosome 2s

genomic differences in 2 types:
1. single nucleotide polymorphisms SNPs
2. large genomic rearrangements

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

single nucleotide polymorphisms (SNPs)

A

Genomic base pair change that helps distinguish one species from another

Most common type of genetic variance among different people

Many or may not result in an amino acid change

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

large genomic rearrangements

A

Larger alterations within the DNA sequence of chromosomes

Inversions:
- A mutation that results from the inversion of a large segment of DNA in a chromosome
- May be as a result of a segmental duplication, transposition of one copy to another arm of the same chromosome and recombination between the 2 segments

Fusions
- The rearrangement of chromosomal DNA by deletion, duplication, insertion, or transposition to form a hybrid gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

outgroups

A

a way to compare genome sequences with those of more distantly related organisms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

comparative genomics

A

researchers assign gene functions by comparing the genomic features of different organisms - can be done with DNA, RNA or protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

homologs

A

2 genes with a demonstrable sequence similarity, whether or not they are closely related by function

Implies an evolutionary relationship

Sequence similarity and a functional relationship go hand-in-hand

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

orthologs

A

Possess a clear sequence and functional relationship to each other

Genes derived from an ancestral gene in the last common ancestor of these 2 species

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

paralogs

A

Genes that are similarly related to each other but within a single species

Arise most often from gene duplication in a single genome, followed by specialization of one or both copies of the gene over the course of evolution

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

the gene unit

A

a single gene is composed of a promoter sequence which defines where transcription will begin, exons and introns

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

splicing

A

process of removing introns from a primary RNA transcript

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

why do simpler organisms not use RNA splicing?

A

Alternative splicing allows multiple, functionally distinct proteins to be encoded by a single gene. This increases protein diversity. Splicing can be specific too certain tissues, conditions, and developmental states. Bacteria and simpler organisms lack intros, and do not undertake alternative splicing. This causes bacteria to lack a level of diversity found in eukaryotes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

chromosome packaging must:

A
  1. be highly organized
  2. allow access to factors that regulate DNA replication
  3. allow access to factors that regulate transcription
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

levels of organization (smallest to biggest)

A

nucleotides, DNA double helix, histones, nucleosomes, chromatin, mitotic chromosome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

histones

A

largest protein component of chromatin

basic, positively charged proteins that assemble into octamers - each octamer unit contains 2 copies of the 4 different histone subunits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

DNA and histones confirmation

A

DNA is wrapped twice around the histone octamers - the positive charge of the histone protein allows them to interact with the negatively charged DNA backbone throuhg electrostatic interations and forms a structure called a NUCLEOSOME

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

organization of the core histones

A

H3 and H4 form a heterotetrameter

each histone octamer has 2 copies of each histone - H2A, H2B, H3, H4

H3 and H4, H2A and H2B is a tetramer that assemble together into an octamer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

H1 unit

A

The DNA that is not wrapped around the histone octamer serves as a linker between nucleosomes. This linker binds the histone H1 unit

H1 binds to the nucleosome and protects the linker DNA from degradation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

what are histones made up of

A

rich in arginine and lysine, making up 25% of any histone protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

nucleosome

A

When the histone octamer binds DNA, it forms a left-handed solenoidal supercoil (an over-wound DNA strand, forming a tightly packed helical structure)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

nucleosome structure

A

Nucleosome structure provides a 6-7 fold compaction of DNA

The DNA is not uniformly bent, but instead follows a pattern of relatively straight 10 base pair segments joined by bends

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

the histone-fold motif

A

A motif for folding is composed of a globular domain that consists of a 3 alpha-helices linked by 2 short loops

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

structural unit of a nucleosome

A

Basic structural unit is composed of a head-to-tail dimer of histone-fold motifs

Due to their 3D structure, each histone-fold dimer forms a V-shaped structure that has 3 DNA-binding sites

The nucleosome will interact with DNA via the minor groove, at all 3 DNA-binding sites

41
Q

AT base pairs influence on nucleosome binding

A

Presence of consecutive A-T (2) and G-C (3) base pairs can influence the ability of DNA to bind the nucleosome

A local abundance of A-T base pairs in the minor groove (where it is in contact with the histones). Facilitates the compression of the minor groove that is needed for tight wrapping of DNA around the histone octamer
ping of DNA around the histone octamer

Histone octamers assemble well with sequences where there is 2 or more A-T base pairs staggered at 10 bp intervals, because DNA is naturally bent at these sequences. A-T base pairs are spaced along the same face of the helix, and DNA bends into a circle

42
Q

GC base pairs influence on nucleosome binding

A

Tracts of G-C base pairs have opposite effects to A-T, where they prevent compression of the minor groove, and are preferred at positions not facing nucleosomes

43
Q

The intermediate

A

DNA –> Nucleosome –> 30 nm filament

44
Q

DNA in the intermediate

A

tightly wraps around an octamer of the histone proteins

45
Q

nucleosome in the intermediate

A

the complex of DNA and a histone octamer

H1 binds to the nucleosome in the DNA linker region

46
Q

30 nm filament in the intermediate

A

after binding of H1, nucleosomes condense into a compact filament with a width of 30 nm

thought to exist in living cells but hasn’t been visualized or proven

47
Q

how does H1 bind to the nucleosome?

A

H1 has 2 DNA-binding sites - 1 to the arm of linker DNA and the other to the central region of the DNA strand in the nucleosome

only one H1 subunit is present per histone octamer unlike the other core histones

48
Q

chromatosome

A

when H1 is bound to the histone octamer and DNA

49
Q

progressive levels of DNA organization in coils

A

DNA –> nucleosome –> 30 nm filament –> extended form of chromosome –> condensed section of chromosome –> mitotic chromosome

50
Q

evidence that DNA is packaged into regularly organized repeating units

A
  1. Kornberg treated chromosomal DNA with a nonspecific DNA nuclease, called micrococcal nuclease, that cuts DNA wherever it is not associated with proteins. The fragments produced were separated by size on an agarose gel
  2. If DNA is packaged by proteins into units of a particular size, the nuclease would cleave only the DNA between these units, and the protected DNA segments (bunded to protein) would migrate in the gel as a ladder of unit-sized bands
    - If proteins were distributed on DNA in a random way, then nuclease digestion would produce a smear of DNA fragments with no regular pattern
  3. Protected DNA segments migrated on the gel as a ladder of regularly-spaced bands
    - Suggests that DNA is packaged by proteins into units that encompass approx. 200 base pairs
51
Q

things to consider for DNA compaction

A
  1. dynamic
  2. modifiable
  3. responsive
52
Q

dynamic in DNA compaction

A

DNA compaction must be dynamic, meaning changes in the degree of condensation must occur quickly and when needed, as cell passes through the stages of the cell cycle

When in its highly compacted form, DNA is not accessible to transcription or replication enzymes so it must be able to rapidly expose regions containing genes that are required at any given moment, and then condense again

53
Q

modifiable in DNA compaction

A

DNA compaction must be globally and locally modifiable

Global = modifications for processes like mitosis or replication

Local = giving access to specific genes for transcriptional regulations

54
Q

responsive in DNA compaction

A

Must be able to respond to modification enzymes that are able to alter the state of DNA condensation

Enzymes can target specific regions for transcription or replication – these regions must be recognizable

55
Q

importance of histone N-terminal tails

A
  • enable organization and compaction of DNA
56
Q

histone N-terminal tails

A

N-termini protrude out from the core particle of the histone and are less ordered - the tails are flexible so they are mostly disordered

they exit through the DNA superhelix through channels formed by the alignment of minor groove

57
Q

H1 vs N-terminal tails

A

H1 is not required for forming the 30 nm filament, but tails are required - meaning the tails provide important nucleosome-nucleosome contacts needed

58
Q

DNA double helix

A

a polynucleotide with a specific sequence of deoxyribonucleotide units covalently joined through 3’,5’-phosphodiester bonds; serves as the carrier of genetic information

59
Q

histone

A

the family of basic proteins that associate tightly with DNA in the chromosomes of all eukaryotic cells and help condense DNA

60
Q

chromatin

A

a thread-like structure, consisting of DNA and histones

61
Q

nucleosome

A

the basic structural unit of chromosomes

62
Q

30 nm filament

A

a condensed version of the nucleosome chain that forms upon binding of the histone H1

63
Q

mitotic chromosome

A

a single large DNA molecule containing a discrete part of the genome-of an organism

64
Q

essential cellular processes that rely on the modification of chromosomes

A
  1. Regulation of gene expression (ex: which genes are actively being expressed in a specific cell)
  2. DNA replication
  3. DNA editing and repair
  4. Recombination events
  5. The preservation of epigenetic tags (a chemical modification that occurs on DNA or specific amino acids in the histone proteins that DNA is wrapped around)
65
Q

the nucleosome and DNA accessibility

A

Nucleosomes control accessibility of DNA to specific proteins, like transcriptional activators or repressors, therefore have a large influence on which genes are actively expressed

Nucleosome arrangements that are more open allow transcription, and closed arrangements repress transcriptions

66
Q

classes of enzymes that regulate chromosome structure

A
  1. chromatin remodeling complexes
  2. histone modifying enzymes
67
Q

chromatin remodeling complexes

A

they open DNA binding sites to allow binding of transcription factors

68
Q

main functions of chromatin remodeling complexes

A
  1. repositions (slide) the nucleosome to a different location along the DNA strand
  2. eject the nucleosome from the DNA
  3. replace the nucleosome with the one that contains a histone variant - variant histone subunits impart special properties to the chromatin
69
Q

different complexes for chromatin remodeling complexes

A

some are preferentially bound, resulting in physical movement - block or expose promoters = repressing or activating transcription OR eject or replace histones

some open up chromatin for gene expression - different ones have different mechanisms of action - some mobilize nucleosomes by forming a DNA loop – causes the nucleosome to slide to a new segment of DNA, enhancing DNA accessibility possibly (exposing a promoter that was previously blocked by the nucleosome)

70
Q

histone modifying enzymes

A

covalently modifies the N-terminal tails of the histone proteins

heritable

cis acting modifications: Modifies the histone molecule directly - May result in opening or closing of the chromatin by tightening or loosening the arrangement of nucleosomes along the DNA

trans acting modifications: Involves other intermediary molecules - Attracts other proteins like transcription factors or chromatin remodeling factors which produce the chromatin change

71
Q

which histone subunits have variants that alter DNA-binding affinity?

A

H2A and H3 have variants that differ in their N- and C- terminal sequences that confer special properties to the chromatin structure

72
Q

H2A variants

A

H2AX, H2AZ, macroH2A - mainly differ in the C- terminal tail region which can recruit various proteins to the nucleosome

73
Q

H2AX

A

DNA repair and genetic recombination

Becomes phosphorylated at Ser139 in the C-terminal region when a double-strand break occurs, attracting DNA repair proteins

If this phosphorylation is blocked, formation of the protein complex for DNA repair is inhibited

74
Q

H2AZ

A

Associated with nucleosomes located at actively transcribed genes

Stabilizes the open state of chromatin, facilitating access of the transcriptional machinery to DNA in actively transcribed regions

75
Q

MacroH2A

A

Abnormally large and contains a unique C-terminal domain

Involved in X chromosome inactivation

Shutting down one of the 2 X chromosomes in female mammals

76
Q

H3 variants

A

H3.3 and CENPA = difference is the susceptibility of residues in the N-terminal tail to modifications such as methylation and phosphorylation

77
Q

H3.3

A

During histone substitutions where active gene expression is occurring

Stabilizes the open state of chromatin, facilitating access of the transcriptional machinery to DNA in actively transcribed regions

78
Q

CENPA

A

A H3 variant

Associated with repeated DNA sequences in centromeres

Contains a large extension that connects to the kinetochore (the site where spindle fibers attach and pull chromosomes apart during cell division)

79
Q

chemical modifications of histones

A
  1. Acetylation of lysine
  2. Methylation of lysine and arginine
  3. Phosphorylation of serine
  4. Ubiquitination of lysine
80
Q

are methylation and acetylation of histone tails reversible

A

yes

81
Q

specific classes of enzymes that can add or remove histone tails

A
  1. HDAC’s (histone deacetylases)
    - Remove the acetyl groups from histones
  2. HATs (histone acetyltransferases)
    - Add acetyl groups to histones
  3. HMTs (histone methyltransferases)
    - Add methyl groups to histones
  4. Jumonji Family (KDMs, histone demethylases)
    - Remove methyl groups from histones
82
Q

specific covalent modifications

A
  1. methylation of arg residues
  2. acetylation of lysine
  3. methylation of lys residues
  4. phosphorylation
83
Q

methylation of arg residues

A

Arginine can be methylated to methylarginine or 2 forms of dimethylarginine; double methylation can result in 1 methyl on each nitrogen of the guanidinium group or 2 methyl’s on one of the nitrogen atoms of the guanidinium group

84
Q

acetylation of lysine

A

Performed by HATs

Acetylate specific residues in a histone tail, neutralizing the positive charge

HDACs will remove acetyl groups

Deacetylation of Lys residues result in transcriptional repression

85
Q

methylation of lys reisudes

A

Methylated to monomethyl, dimethyl, trimethyllysinne

Lys9 or Lys14 of H3 can either be methylated or acetylated

86
Q

phosphorylation

A

Commonly found on histone tails of H3 and H4

Can only occur on Ser, Thr, or Tyr residues because they have a hydroxyl group

Adds a negative charge to the tail

87
Q

3 ways to alter chromatin structure/accessibility by modifying the nucleosome

A
  1. Chromatin remodeling complexes
    - Reposition, eject or replace a nucleosome on the DNA strand
  2. Variant histones that replace core histones within the nucleosome, influencing the chromatin structure
  3. Chemical modifications by histone modifying enzymes to the histone tails
    - Acetylation or methylation, which alters chromatin structure
88
Q

chromatin immunoprecipitation (ChIP) steps

A
  1. Cells are treated with formaldehyde to covalently crosslink nucleosomes to DNA. The cells are then disrupted, and genomic DNA is digested with micrococcal nuclease (an endo-exonuclease that preferentially digests single-stranded nucleic acids)
  2. An antibody to a specific modified histone is then used to immunoprecipitate the nucleosome-DNA complex. Any DNA not bound to a histone is washed away
  3. Protein-DNA crosslinks are reversed by heating and the released DNA is analyzed. If associations with a specific segment of the genome are suspected, DNA from this region can be amplified/quantified by PCR or qPCR. Otherwise, the released DNA can be sequenced (ChIP-Seq)
  4. Alternatively, the released DNA is labeled and used to probe a microarray. The pattern of hybridization on the array reveals the DNA sequences that associate with the nucleosomes (ChIP-Chip)
89
Q

chromatin immunoprecipitation (ChIP)

A

technique used to determine the specific interactions between DNA and a protein, like a transcription factor

determines where on DNA sequence a protein exactly binds to

90
Q

how do chromatin states get stabilized

A
  1. bromodomains
  2. chromodomains
91
Q

bromodomains as enzymes to stabilize chromatin states

A

Recognize the acetylated Lys residues

Usually contained within a larger, multiprotein complex like the chromatin remodeling complex

If a chromatin remodeling complex contains a subunit with both a bromodomain and histone acetylase activity, the complex binds to an acetylated nucleosome so that a specific pattern of acetylation can be propagated in a targeted area of the chromosome

Leads to higher levels of gene expression

92
Q

chromodomains as enzymes to stabilize chromatin states

A

Proteins that bind to methylated Lys residues

Often found in complexes with other enzymes that further modify chromatin structure

93
Q

open vs closed chromatin states

A
  1. Acetylated nucleosomes are recognized by bromodomain proteins that may help stabilize the open chromatin state
  2. Methylated histones are recognized by chromodomain proteins that may help promote the closed state
94
Q

epigenetic inheritance

A

the study of heritable changes in gene function that do not involve changes in the DNA sequence

95
Q

where can epigenetic inheritance be transferred to

A
  1. from parent cells to daughter cells during division
  2. intergenerationally (between generations) between organisms from parents to their offspring
96
Q

propagation of histone modifications

A
  1. epigenetic modifications during development
  2. controlling epigenetic modifications
  3. epigenetic modifications
97
Q

H3-H4 tetramers during replication

A

remain bound to the DNA, unlike histone octamers that split apart during replication

98
Q

marked histones during replication steps

A
  1. H3-H4 are randomly distributed on the 2 new daughter DNA duplexes made during replication, and coat only half of the total DNA after replication
  2. The new H3-H4 heterotetramers that lack the modification pattern of those they will replace are assembled onto the replicated DNA by the CAF-1 chaperone protein
  3. Parental H2A-H2B dimers remain in vicinity after being displaced by the replication fork and quickly reassemble with H3-H4 heterotetramers onto the newly replicated DNA, chaperoned by NAP-1. New, unmodified H2A-H2B dimers must be assembled on the newly replicated DNA
  4. 4 types of nucleosomes form on the daughter DNA strands:
    - Old/parental H3-H4 and new H2A-H2B
    - New H3-H4 and old H2A-H2B
    - Entirely parental of H2A-H2B-H3-H4 histones
    - Entirely new H2A-H2B-H3-H4 histones
  5. The newly replicated DNA has only half of the parental epigenetic information on its histones, but the daughter DNA duplexes are “salted” with the parental histone modification pattern

BCHM218 (4 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions