TY - JOUR
T1 - Stochastic gene expression and chromosome interactions in protecting the human active X from silencing by XIST
AU - Migeon, Barbara R.
N1 - Publisher Copyright:
© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021
Y1 - 2021
N2 - Mammals use X chromosome inactivation to compensate for the sex difference in numbers of X chromosomes. A relatively unexplored question is how the active X is protected from inactivation by its own XIST gene, the long non-coding RNA, which initiates silence of the inactive X. Previous studies of autosomal duplications show that human chromosome 19 plays a critical role in protecting the active X. I proposed that it genetically interacts with the X chromosome to repress XIST function on the future active X. Here, I show that the type of chromosome 19 duplication influences the outcome of the interaction: the presence of three chromosome 19s is tolerated whereas duplications affecting only one chromosome 19 are not. The different outcomes have mechanistic implications for how chromosome 19 interacts with the future active X, pointing to a role for stochastic gene expression and possibly physical interaction.
AB - Mammals use X chromosome inactivation to compensate for the sex difference in numbers of X chromosomes. A relatively unexplored question is how the active X is protected from inactivation by its own XIST gene, the long non-coding RNA, which initiates silence of the inactive X. Previous studies of autosomal duplications show that human chromosome 19 plays a critical role in protecting the active X. I proposed that it genetically interacts with the X chromosome to repress XIST function on the future active X. Here, I show that the type of chromosome 19 duplication influences the outcome of the interaction: the presence of three chromosome 19s is tolerated whereas duplications affecting only one chromosome 19 are not. The different outcomes have mechanistic implications for how chromosome 19 interacts with the future active X, pointing to a role for stochastic gene expression and possibly physical interaction.
KW - 19p trisomies
KW - 3-D nuclear interactions
KW - X chromosome inactivation
KW - X/autosome interactions
KW - protecting the active X from XIST silencing
KW - stochastic gene expression
UR - http://www.scopus.com/inward/record.url?scp=85099687667&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85099687667&partnerID=8YFLogxK
U2 - 10.1080/19491034.2020.1850981
DO - 10.1080/19491034.2020.1850981
M3 - Article
C2 - 33211621
AN - SCOPUS:85099687667
VL - 12
SP - 1
EP - 5
JO - Nucleus
JF - Nucleus
SN - 0115-2300
IS - 1
ER -