Chromatin structure and gene expression, including epigenetics Flashcards
Describe the different states of chromatin condensation”
- euchromatin
- heterochromatin
Describe euchromatin
- “beads on a string”
- 11nm fiber - actively transcribed genes
Describe heterochromatin
- 30nm chromatin fibre of packaged nucleosomes
- extended and condensed into a mitotic chromosome
- not transcribed
Describe the function euchromatin
DNA accessible for transcription
Describe the function heterochromatin
DNA inaccessible for transcription
Describe the fundamental building block of chromatin
Nucleosomes
Describe histones
- 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
Describe the two major factors regulating chromatin condensation
- histone H1
- post-translational modifications of “histone code”
Describe histone H1
- “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
“histone code”
histone tails
Describe histone tails
- 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
K
lysine
R
arginine
acetylation
removes the basic charge of K or R residue
Describe acetylation
removes the basic charge of K or R residue
Describe methylation
does not affect charge of K or R residue
Describe acetylated histone tails
- form weaker interaction with DNA
- chromatin loosened/decondensed
- associated with transcription
Describe methylated histone tails
- interaction with DNA not directly disrupted
- changes histones affinity for different histone binding proteins
- different methylation states can either enhance or repress transcription
How many possible combinations of acetylation/methylation are there
1013
Different combinations of histone modifications are found in…
different regions of the genome
How many nucleosomes are required to pack diploid human genome
3 x 10^7
Give some regions of the genome
- telomeres
- centromeres
- retrotransposons
- microsatellites
- genes
- exons
- introns
- promoters
Different combinations of histone marks result in
different condensation states of chromatin AND result in differential recruitment of other proteins
Describe the function of histones in promotor regions
recruit histone acetylases and nucleosome remodellers e.g. SWI/SNF
Describe epigenetics
daughter cells inherit the chromatin accessibility profile and therefore gene expression profile of their parent cell
Describe inheritance
1) Histone code
2) RNA and protein made by parent cell
3) DNA methylation
Describe over-expressed KMD1A during sperm formation in mice
- 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
KMD1A
H3K4 demethylase
Chromatin is made of …
nucleosomes
Nucleosomes made of
histones
Histones have “tails” that can be modified to
influence DNA binding and recruitment of other proteins.
The histone code
regulates chromatin condensation and transcription
