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Hello, I'm Susan Gasser.
And I'm going
to you speak to you today
about Gene Silencing
in Budding Yeast.
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Gene silencing
is an epigenetic phenomenon
whereby a gene is silenced
or not transcribed
in a manner that is heritable
from one cell to the next.
In the lower right-hand corner,
you see colonies of yeast
where a gene that will turn
the yeast cell red
is either expressed
or not expressed
in these colonies.
The sectoring shows
heritable repression.
The same phenomenon occurs
in the eye of the Drosophila
when a gene is transferred
or emplaced
near centromeric head
or chromatin.
Today, I'll explain
how this phenomenon occurs.
0:44
First of all, our genome
is made-up of DNA
complexed with histone proteins
in a complex called chromatin.
This protein DNA complex
carries an additional level
of organization
and information in an epigenome.
When the histone tails
are acetylated
or transcription factors
are bound,
we call this euchromatin,
it's accessible and plastic
to transcription machinery
and usually
transcriptionally active.
On the other hand,
if the histone tails
are methylated,
the other proteins bind,
turning this chromatin
into heterochromatin.
It is inaccessible.
It shows restricted expression
and can be inherited
in a silent state.
1:30
The active chromatin is composed
of a number of modifications
across all species correlated
with active genes.
Histone H3 can be methylated
on lysine 4,
on lysine 36,
and the histone H4 tail
can be acetylated
on a number of lysine residues.
These modifications
attract nucleosome remodelers
which they can shift or evict
nucleosomes, and finally,
is the binding of proteins
that keep the domain
in an active state.
In repressed chromatin,
histone tails are modified
with other kinds
of modifications.
Histone H3 is modified
by methylation on lysine 9
or lysine 27,
and histone H4 on lysine 20.
These methylation sites
can attract repressive proteins
that then mask
the DNA polymerases
from the activity
of transcription.
In higher eukaryotes,
cytosine residues
become methylated
and this correlates
with a repressed state
as well as the stable binding
of general repressors.
Finally, in some species,
double-stranded RNAs
are transcribed
from heterochromatic regions
and this again nucleates
repression of the genes.
In budding yeast,
which we'll be talking
about today,
all the modifications
here listed are present
and they're conserved
from yeast to man.
The phenomenon, however,
of active or inactive chromatin
is largely the same.
So why should we study silent
heterochromatin
in a small organism
like budding yeast?
