lecture 10 Flashcards
Are mitotic or interphase chromosomes more compacted?
mitotic are much more compact than interphase chromosomes
The DNA in chromatin is tightly associated with proteins called
histones
histones package and order the DNA into structured units called
nucleosomes
(a fundamental unit of chromatin “beads-on-a-string”)
histone
small proteins associated with DNA
which amino acids would you expect histones to be rich in?
basic amino acids
how is the nucleosome formed
DNA is wrapped around the histone core to form the nucleosome
histone H1 clamps around the DNA
describe histone interaction with DNA
not specific
Histone N-terminal tails (4 characteristics)
-protrude from the octameric disk
-highly-conserved between histones
-positively charged w many Lys and Arg residues: basic amino acids (good bc DNA is negative)
-highly flexible
Histones (4 characteristics)
-determine the structure of the nucleosome
-treat DNA w nuclease
-DNA bound to the histone is protected from degredation
-the core can be dissociated by high [salt] concentration
When you add high concentration of salt to histone
DNA dissociates from histone
30nm chromatin fiber of packed nucleosomes
the beads-on-string coil to form 30nm chromatin fibers
also known as 30nm chromatin fibers or “solenoid”
H1 holds the DNA on the
histone core
H1 is necessary for the formation of
the 30nm fiber
-contains a long pair of flexible tails
-H1 is located in the interior of the 30nm fiber
Regions of the DNA that are transcriptionally active are
less well ordered and contain very little histone H1
does transcription occur in the 30nm fiber?
no
compaction makes the DNA inaccessible to transcription and replication factors
N-terminals and the 30nm fiber: interactions
Histone tails may help pack nucleosomes into the 30nm fiber
+ charged N-termini bind (-) charged sugar-phosphate backbone on DNA of neighboring nucleosomes
The 30nm fiber is held together by (2)
- histone H1 proteins which “pull” the nucleosomes together
- N-terminal tails
High order of chromatin organization
not well understood!!
-further looping/coiling of solenoid DNA into highly compacted, transcriptionally silent, form of chromatin occurs during mitosis
-certain regions of the DNA associate with a nuclear or chromosome “scaffold”
Chromatin remodelling complexes
protein machines that use ATP to change the position of DNA wrapped around nucleosomes
-makes the DNA more OR less accessible!!!
How does the cell remodel to change the compaction and gene expression
modification of histones
-histone code
histone code
hypothesis that specific combinations of modifications dictate gene expression or silencing
-works with chromatin-remodelling complexes
-covalent modifications may act as a docking site for regulatory proteins
Histone tails are often —- that results in changes in chromatin structure (and example)
covalent modifications
-ex. addition of acetyl phosphate or methyl groups
Interphase chromatin is
not uniformly packed, contains regions that are expressed more or less often
2 forms of interphase chromatin
Heterochromatin= most highly condensed form
Euchromatin= the rest of the interphase chromatin
Heterochromatin can
spread
heterochromatin-specific modifications can
recruit proteins that will make the same modifications
will continue making these modifications until it is blocked by a barrier DNA sequence
Heterochromatin and disease (and example)
if an important gene is appropriately packaged into heterochromatin, there would be limited gene expression!!!!
ex. deficiency of beta-globin causing anemia (affects level of DNA compaction)
Female mammal X chromosomes
they have two X chromosomes:
-only one is active
-the other is inactivated (at random) by condensing it into heterochromatin
-All daughter cells inherit the same histone modification
example of epigenetic inheritance
transmission of a pattern of gene expression from one cell to the cells it creates that does not involve altering the nucleotide sequence of the DNA
Mutations in a gene on the X chromosome result in a particular form of colour blindness. If a woman if colourblind, what can we conclude about her father?
If the woman is colourblind, she has a mutation in this gene on both X chromosomes meaning that the father must be colourblind.
Would you expect her mother to be colourblind too? If no, would she have normal colour vision?
The mother could be colourblind and be carrying two defective copies. She might only have one defective copy. It’s also possible that she has one defective copy and may see coloured objects with reduced resolution.
less compact chromatin means
more gene activity
