Chromatin structure and gene expression, including epigenetics Flashcards

1
Q

Describe the different states of chromatin condensation”

A
  • euchromatin
  • heterochromatin
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2
Q

Describe euchromatin

A
  • “beads on a string”
  • 11nm fiber - actively transcribed genes
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3
Q

Describe heterochromatin

A
  • 30nm chromatin fibre of packaged nucleosomes
  • extended and condensed into a mitotic chromosome
  • not transcribed
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4
Q

Describe the function euchromatin

A

DNA accessible for transcription

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5
Q

Describe the function heterochromatin

A

DNA inaccessible for transcription

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6
Q

Describe the fundamental building block of chromatin

A

Nucleosomes

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7
Q

Describe histones

A
  • histone octamer forms a barrel from two of each of H2A, H2B, H3 and H4
  • unstable in the absence of DNA
    147 bp of DNA to wrap twice around a nucleosome
  • “tails” of each histone monomer extend out from the nucleosome
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8
Q

Describe the two major factors regulating chromatin condensation

A
  • histone H1
  • post-translational modifications of “histone code”
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9
Q

Describe histone H1

A
  • “The linker histone”
  • binds to histone octamer by linker DNA, with histone tails extended out
  • stabilises chromatin, increasing condensation
  • important for formation of 30nm fiber
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10
Q

“histone code”

A

histone tails

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11
Q

Describe histone tails

A
  • lots of basic residues – K and R
  • positive charge at neutral pH
  • when histone tails interact with DNA, more condensed chromatin
  • residues can be modified by acetylation or methylation
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12
Q

K

A

lysine

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13
Q

R

A

arginine

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14
Q

acetylation

A

removes the basic charge of K or R residue

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15
Q

Describe acetylation

A

removes the basic charge of K or R residue

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16
Q

Describe methylation

A

does not affect charge of K or R residue

17
Q

Describe acetylated histone tails

A
  • form weaker interaction with DNA
  • chromatin loosened/decondensed
  • associated with transcription
18
Q

Describe methylated histone tails

A
  • interaction with DNA not directly disrupted
  • changes histones affinity for different histone binding proteins
  • different methylation states can either enhance or repress transcription
19
Q

How many possible combinations of acetylation/methylation are there

A

1013

20
Q

Different combinations of histone modifications are found in…

A

different regions of the genome

21
Q

How many nucleosomes are required to pack diploid human genome

A

3 x 10^7

22
Q

Give some regions of the genome

A
  • telomeres
  • centromeres
  • retrotransposons
  • microsatellites
  • genes
  • exons
  • introns
  • promoters
23
Q

Different combinations of histone marks result in

A

different condensation states of chromatin AND result in differential recruitment of other proteins

24
Q

Describe the function of histones in promotor regions

A

recruit histone acetylases and nucleosome remodellers e.g. SWI/SNF

25
Q

Describe epigenetics

A

daughter cells inherit the chromatin accessibility profile and therefore gene expression profile of their parent cell

26
Q

Describe inheritance

A

1) Histone code
2) RNA and protein made by parent cell
3) DNA methylation

27
Q

Describe over-expressed KMD1A during sperm formation in mice

A
  • loss of H3K4 methylation at more than 2000 genes
  • methylation loss persisted for 3 generations even though they no longer had KDM1A gene expression
  • all 3 generations had abnormal development
28
Q

KMD1A

A

H3K4 demethylase

29
Q

Chromatin is made of …

A

nucleosomes

30
Q

Nucleosomes made of

A

histones

31
Q

Histones have “tails” that can be modified to

A

influence DNA binding and recruitment of other proteins.

32
Q

The histone code

A

regulates chromatin condensation and transcription