Ch. 4 pt 1 and Ch. 4 pt 2 Flashcards

ch. 4 pt 1: 22-32; Ch. 4 pt 2: 1-9

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1
Q

only about 20% of the genome is….

A

packaged in that portion of the euchromatin associated with the actively expressed genes

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2
Q

20% open, active chromatin can be broken down into…

A

8%- highly accessible promoters, enhancers, active genes

12%- weakly transcribed genes

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3
Q

inactive, closed chromatin is __% euchromatin and __% heterochromatin

A

40 and 40

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4
Q

the 40% of inactive, closed euchromatin is…

A

quiescent, unmarked, linker histone bound

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5
Q

the 40% of inactive, closed heterochromatin is broken into

A

20%- facultative heterochromatin, regulated

20%- constitutive heterochromatin, permanent

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6
Q

facultative heterochromatin, regulated: includes?

A

developmentally repressed genes

marked by H3K27me3 or H3K9me

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7
Q

constitutive heterochromatin, permanent: includes

A

centromeres, telomeres, satellites, other repeats

marked by H3K9me3

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8
Q

chromatin modifiers

A

chemically alter histone proteins in the nucleosome by adding chemical groups to amino acid side chains or by removing them

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9
Q

chromatin modifiers primarily occur at…

A

N-terminal histone tails

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10
Q

chromatin modifiers: modifications include…

A

acetylation
methylation
phosphorylation
ubiquitination
others

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11
Q

histone modifications impact…. and….

A

impact chromatin structure and play a role in gene expression

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12
Q

two main mechanisms by which histone modifications exert their effects

A

directly influencing chromatin structure

building effector molecules to regulate gene expression and other cellular activities

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13
Q

modifications recruit…

A

proteins to alter chromatin structure and regulate gene activity

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14
Q

acetylation _____ chromatin

A

opens

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15
Q

nomenclature:

H3K27me3

A

H3: histone 3
K27: lysine; 27th amino acid
me3: 3 methyl groups

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16
Q

histone modification : H4K4me3

associated with chromatin type:

gene expression:

abundance:

A

histone modification: methylation

associated with chromatin type: highly accessible, open chromatin

gene expression: ON

abundance: 1%

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17
Q

histone modification : H3K9ac

associated with chromatin type:

gene expression:

abundance:

A

histone modification : acetylation

associated with chromatin type: highly accessible, open chromatin

gene expression: ON

abundance: 1%

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18
Q

histone modification : H3K9me3

associated with chromatin type:

gene expression:

abundance:

A

histone modification : methylation

associated with chromatin type: heterochromatin (constitutive or facultative)

gene expression: OFF

abundance: 25%

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19
Q

histone modification : H3K27me3

associated with chromatin type:

gene expression:

abundance:

A

histone modification : methylation

associated with chromatin type: facultative heterochromatin

gene expression: OFF

abundance: 13%

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20
Q

the histone code is a well established hypothesis describing the idea thatspecific patterns of post translational modifications to histones act like a __________ recognized and used by non hisotne porteins to regulate specific ___ functions

A

molecular “code”

specific chromatin functions

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21
Q

the histone code should be considered to be more like a …

A

language

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22
Q

writer reader and eraser proteins

A

writer: chemically modifies the histone

reader: effects the execution of the appropriate biological function

eraser: removes the histone modification

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23
Q

all of the covalent additions to histones are_______, being constantly removed and added at rates that depend on both their _______ locations and specific ______ of the cell.

A

dynamic; chromosomal; states

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24
Q

acetylation writers and erasers

A

writer: histone acetyltransferase (HAT)

eraser: histone deacetylase (HDAC)

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25
Q

methylation writers and erasers

A

writer: histone methyltransferase (HMT)

eraser: histone demethylase (HDMT)

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26
Q

methylation may promote activation or repression depending on…

A

location

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27
Q

initially, sequence specific DNA binding proteins (e.g transcription factors) may…

A

bind DNA and recruit the histone modifying enzymes.

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28
Q

transcription regulator (transcription factor)

A

general name for any protein that binds to a specific DNA sequence to influence the transcription of a gene

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29
Q

a generalized sequence of events for activating transcription:

  1. _____________________ binds DNA
  2. ______ (writer) binds to TF and ________ the histones in the vicinity (nucleoside associate loosens)
  3. chromatin remodeling complex ___ the nucleosome, allowing access to the DNA
  4. addition ____- bind
  5. _____________ binds and transcription begins
A
  1. transcription factor
  2. HAT (writer); acetylates
  3. slides the nucleosome, allowing access to the DNA
  4. TFs
  5. RNA polymerase
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30
Q

reader-writer

after a writer enzyme modifies one or a few nucleosomes…

A

the writer collaborates with a reader in the same protein complex to spread the modification from nucleosome to nucleosome

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31
Q

reader-eraser

A

a reader eraser complex can reverse the chromatin change

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32
Q

barrier DNA sequences

mark the boundaries of….

barrier DNA-protein complexes block the spread of…

A

-chromatin domains
- reader-writer complexes

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33
Q

two major classes of heterochromatin in mammalian cells

A

facultative heterochromatin
-trimethylation of H3K27
-highly regulated

constitutive heterochromatin
-trimethylation of H3K9
-permanent

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34
Q

function of constitutive heterochromatin

A

-form the centromere
-silence a variety of selfish DNA elements
-tightly repress genes that are active early in embryonic development

35
Q

centromeric chromatin

A

-location of cetromere
-constitutive heterochromatin
-persists throughout interphase
-contains a centromere-specific variant H3 histone: CENP-A
-CENP-A plus additional proteins form the kinetochore

36
Q

human centromeres

A

-over several million nucleotide pairs
-do not contain centromere-specific DNA sequence
-largely consist of short repeated DNA sequences
-there is plasticity of centromere formation

37
Q

faithfully inherited…

A

once a special region of chromatin forms, this assembly is thereafter faithfully inherited

38
Q

epigenetic inheritance

A

inheritance of phenotypic changes in a cell or organism that do not result from changes in the nucleotide sequence of DNA

39
Q

epigenetic inheritance can be due to…

A

positive feedback loops of transcription regulators or to heritable modifications in chromatin such as DNA methylation of histone modification

40
Q

chromosomes occupy…

A

discrete territories in the nucleus

41
Q

chromosomes are or are not extensively entangled with one another

A

are not

42
Q

how are heterochromatin and euchromatin distributed differently?

A

heterochromatin is often closely associated with the nuclear envelope

euchromatin extends into the nucleoplasm bay from the nuclear envelope

43
Q

heterochromatin:
_____ nearest to periphery
_____ interior to ^

A

H3K9me3

H3k27me3

44
Q

dynamic structure of interphase chromosomes

A

loops of chromatin expand to occupy an increased volume when a gene within them is expressed

45
Q

the interior fo the nucleus is very ____, with functionally different regions to speed different biochemical processes

A

heterogeneous

46
Q

topologically associating domains (TADs)

A

fundamental units of 3D nuclear organization

47
Q

interphase chromosomes are organized as…

A

long linear series of folded looped domains of chromatin (TADs)

48
Q

roughly ____ loops in the human genome

between _____ - ______ nucleotide pairs of DNA, though loops of a million nucleotide pairs also exist

A

10,000

50,000-200,000

49
Q

DNA sequences within a TAD…

A

physically interact with each other more frequently than with sequences outside of that domain

50
Q

TADS partition the genome into

A

distinct regulatory territories

51
Q

TADS: likely function in regulation of gene expression by…

A

limiting enhancer-promoter interactions to sequences with a TAD

52
Q

TADs: loop positions can fluctuate, allowing for…

A

a highly dynamic chromatin structure during interphase

53
Q

disruption of TAD boundaries may result in…

A

a wide range of diseases

54
Q

TAD: the loop extrusion model involves the…

A

cohesion complex to generate loops and CTCF protein to establish the boundaries of the loops

55
Q

SMC proteins are a family of …. that…

A

family of large ATPases that participate in many aspects of higher order chromosome organization and dynamics

56
Q

SMC stands for

A

structural maintenance of chromosomes

57
Q

SMC proteins form…

A

distinct heterodimers that make the core components of multi protein complexes such as cohesion and condensin

58
Q

cohesin: ____ and ____

A

SMC1 and SMC3

59
Q

condensin: ______ and ________

A

SMC2 and SMC4

60
Q

what is a SMC protein complex?

A

a large ring shaped protein complex that uses ATP hydrolysis energy to make the looped domains that organize chromosomes

61
Q

SMC protein complexes include

A

the eukaryotic cohesin and condensin proteins

62
Q

SMC protein complexes have important roles in….

A

bacteria, archaea, and eukaryotes

63
Q

the SMC protein is a large protein of ___ to_____ amino acids that folds on itself to form antiparallel coiled coil with a globular head. two of these molecules then pair to produce a ring structure with a ____ at one end an an ___ binding domain at the other end. additional subs are then added to for either __ or ____.

A

1,000 to 1,5000
flexible hinge
ATP
cohesin or condensin

64
Q

SMC protein complexes bind and encircle the..

A

DNA double helix

65
Q

the SMC heterodimers forms a ring that is large enough for…

A

DNA that is packed in chromatin to readily pass through

66
Q

the SMC ATPase domains allow the ring to…

A

motor rapidly along DNA

67
Q

the cohesin complex is a protein complex that mediates

A

DNA looping
sister chromatid cohesion
homologous recombination
other cellular processes

68
Q

cohesin complexes have different subunit compositions for…

A

different functions

69
Q

text definition of cohesin complex

A

complex of proteins that uses ATP hydrolysis energy to organize interphase chromosomes into a series of looped domains

70
Q

during mitosis, cohesins also…

A

hold sister chromatids together along their length before their separation

71
Q

mechanism of TAD formation: loop extrusion model

  1. the cohesin complex binds ___ to form a _________.
  2. using the energy of _________, cohesin extrudes chromatin on both sides of the ring to ____ the loop
  3. cohesin stops when it encounters a chromatin bound ________ protein on each side.
A
  1. chromatin; small DNA loop
  2. ATP hydrolysis; enlarge
  3. CTCF
72
Q

TAD boundaries are brought together with….

A

CTCF complexes forming the base of a chromatin loop

73
Q

mitotic chromosomes are _______

A

highly condensed

74
Q

chromosome folding in M phase:

  1. chromatin loops created by cohesin are…
  2. ________ begins to form very large chromatin loops organized radially by a ….
  3. as _______ loops grow larger, ______ forms a second set of loops within the larger loops. this generates a loops within loops organization
  4. along with tighter winding of chromatin loops around the ________, a very compact chromatin is created
A
  1. quickly lost
  2. Condensin II; central chromosome axis
  3. condesin II, condesin I
  4. mitotic chromosome axis
75
Q

genome comparison reveal functional DNA sequences by their….

A

conservation throughout evolution

76
Q

homologous genes

A

genes that are similar in both their nucleotide sequence and function because of a common ancestry

77
Q

homologous genes can often be recognized across vast….

A

phylogenetic differences

78
Q

in general, the sequences of individual genes are much more tightly conserved than is overall ___ structure

A

genome

79
Q

DNA sequences that are closely similar between different species are through to more likely ….

A

have a functional conserved DNA regions

80
Q

conserved DNA regions

A

closely similar pieces of DNA sequence

81
Q

______% of the human genome consists of multi species conserved sequences

A

4.5%

82
Q

about 1% of multi species conserved species….
the remaining….

A

code for proteins
the remaining :
-protein binding site for gene regulation
-transcribed into important non coding RNAs

83
Q

an additional 5% of our genome shows a …….., implying that these sequences are also important

A

reduced variation in the human population