Epigenetics IV: X-chromosome inactivation Flashcards
What lead to dosage imbalances between homogametic and heterogametic sexes?
Dimorphic sex chromosomes
What are some properties of the inactive X chromosome (Xi)?
Compact structure, nuclear periphery, epigenetically inherited, H3K27me, H3K9me, hypoacetylation of histones, DNA methylation and Xist non-coding RNA
When does X-chromosome inactivation occur?
It randomly occurs in the embryo and is coincident with onset of differentiation
XCI occurs first specifically in the _____________ and affects the paternal X
Trophectoderm
Choice of which X is inactivated appears to be (chosen/random)
Random
Where does X-chromosome reactivation occur?
PGCs
Mosaicism is (epigenetic/genetic)
Epigenetic
What region of the chromosome allows X inactivation?
X inactivation center (Xic)
What is the role of Xist?
Coats the Xi and causes silencing in cis
Which cells can be used to study XCI?
Embryonic stem cells
How is Xist regulated?
Cis factors on the X chromosome and trans factors on the autosomes
Xist is regulated by (sense/antisense) transcription
Antisense
What is the negative regulator of Xist?
Tsix
Xist is detected by (sense/antisense) probes and Tsix is detected by (sense/antisense) probes
Sense; antisense
Removal of Tsix promoter from one X causes what effect for Xist?
Xist is activated in that X chromosome
X lacking Tsix is always (activated/inactivated)
Inactivated
In males only (Xist/Tsix) is expressed
Tsix
What represses the action of Xist?
Pluripotency transcription factors
Rnf12 is an enzyme that is encoded on the X chromosome and causes the degradation of which trans transcription factor?
Rex1
True or false: Degradation of Rex1 by Rnf12 causes X inactivation
True
What are the general approaches for defining functions of Xist RNA?
Genetics and biochemistry
Identify the results to the deletion of a Xist RNA repeat
a. No repression of transcription, but Xist can still localize to the X chromosome, recruitment of SPEN
b. No Xist localization to inactive X, repression compromised
c. No PRC association or H3K27me on inactive X but repression can still happen
a. Delete A repeat
b. Delete E repeat
c. Delete C repeat
True or false: XCI requires Xist for maintenance
False
What does stable maintenance of XCI in the embryo require?
DNA methylation by DNMT1 and DNMT3B and hypoacetylation of histones
CGI is (unmethylated/methylated) at promoters on inactive X
Methylated
Where does reactivation of the inactive X occur?
PGCs
