XCI Flashcards
genes responsible for Xist control
There are ‘numerators’ and
‘denominators’ that control the expression of Xist. There is a tight balance between
the numerators and denominators. Numerators activate Xist while denominators
repress it.
are
Nanog, Sox2 and Rex1 numerators or denominators
ESCs have 2 active X chromosomes, this means that Xist is shutdown. ESCs also express
the pluripotency markers Oct4, Nanog, Rex1 and Sox2. Upon differentiation, Xist is
upregulated because 1 X chromosome is randomly chosen for inactivation. Also, the
expression of the pluripotency factors go down because cells are exiting the
pluripotency stage (they are differentiating). Pluripotency factor expression
anticorrelates then with Xist expression. I would say that pluripotency factors are
repressing Xist in the ESC stage, they are denominators. They are encoded in
autosomes.
Activating or repressing ?
H3K27ac
activating
Activating or repressing ? H4K3me1/2/3
activating
Activating or repressing ? H3K27me3
repressing
Activating or repressing?
H2AK119Ub
repressing
Activating or repressing ?
meCpG
repressing
Describe the general Xist cascade
Xist starts then spreading in cis and recruits many inhibitory proteins, such as SPEN,
which recruits HDAC3. HDAC3 removes acetylation marks, while SPEN recruits SMRT, a
repressor. Xist also recruits PRC2 which puts H3K27me3, and H3K27me3 recruits PRC1
which puts H2AK119Ub. All of this leads to DNMT1 recruitment and CpG methylation
to shut down expression. H2A is also substituted by macroH2A.
Where is inactivated X generally located
periphery of nucleus, close to the lamina where stuff is inactivated
are activating marks removed before or after the
repressive marks are installed
Activating marks seem to be removed before the repressive marls are put down.
HDAC3 removes H3K27ac. Then comes PRC2 to put H3K27me3, then this attracts
PRDC1 which puts down H2AK119ub. Eventually, at last, mCpG appears.
some escapees escape XCI in one tissue but not in others. True or False
True
Two ways of escaping X-inactivation
- They loop out of the silenced nuclear compartment that the inactive X is. In other
words, the Xi generates a compact, heterochromatic environment and escapees loop
out of them. - CTCF/cohesin might be present to for a boundary around the escapee. This prevents
the Xi (facultative) heterochromatin to move in on the escapee.
Both hypothesis here above have been confirmed for some escapees.
The n-1 rule defends that all X chromosomes in a cell are inactivated but one,
per autosome pair. Select the correct statement:
a. This is because after the denominators on the X chromosomes are
inactivated, the balance of numerators vs denominators goes back to an
equilibrium where additional Xs cannot be inactivated.
b. This is because after the numerators on the X chromosomes are
inactivated, the balance of numerators vs denominators goes back to an
equilibrium where additional Xs cannot be inactivated.
c. A tetraploid female cell will inactivate 3 chromosomes and retain a
single active X chromosome.
d. The n-1 rule is dependent on lncRNAs only.
b
Escapees tend to be located:
outside of the repressive compartment of the inactive X chromosome duhh