TY - JOUR
T1 - Differentiation-dependent requirement of Tsix long non-coding RNA in imprinted X-chromosome inactivation
AU - Maclary, Emily
AU - Buttigieg, Emily
AU - Hinten, Michael
AU - Gayen, Srimonta
AU - Harris, Clair
AU - Sarkar, Mrinal Kumar
AU - Purushothaman, Sonya
AU - Kalantry, Sundeep
N1 - Funding Information:
We thank Miriam Meisler, David Burke, John Moran and members of the Kalantry Lab for discussions of the manuscript. We acknowledge the services of the University of Michigan Sequencing Core Facility, supported in part by the University of Michigan Comprehensive Cancer Center. This work was funded by an NIH National Research Service Award #5-T32-GM07544 from the National Institute of General Medicine Sciences to E.M.; an NIH Pathway to Independence Award (R00HD055333) to S.K.; an NIH Director’s New Innovator Award (DP2-OD-008646-01) to S.K.; a March of Dimes Basil O’Connor Starter Scholar Research Award (5-FY12-119); and the University of Michigan Endowment for Basic Sciences.
PY - 2014/6/30
Y1 - 2014/6/30
N2 - Imprinted X-inactivation is a paradigm of mammalian transgenerational epigenetic regulation resulting in silencing of genes on the paternally inherited X-chromosome. The preprogrammed fate of the X-chromosomes is thought to be controlled in cis by the parent-of-origin-specific expression of two opposing long non-coding RNAs, Tsix and Xist, in mice. Exclusive expression of Tsix from the maternal-X has implicated it as the instrument through which the maternal germline prevents inactivation of the maternal-X in the offspring. Here, we show that Tsix is dispensable for inhibiting Xist and X-inactivation in the early embryo and in cultured stem cells of extra-embryonic lineages. Tsix is instead required to prevent Xist expression as trophectodermal progenitor cells differentiate. Despite induction of wild-type Xist RNA and accumulation of histone H3-K27me3, many Tsix-mutant X-chromosomes fail to undergo ectopic X-inactivation. We propose a novel model of lncRNA function in imprinted X-inactivation that may also apply to other genomically imprinted loci.
AB - Imprinted X-inactivation is a paradigm of mammalian transgenerational epigenetic regulation resulting in silencing of genes on the paternally inherited X-chromosome. The preprogrammed fate of the X-chromosomes is thought to be controlled in cis by the parent-of-origin-specific expression of two opposing long non-coding RNAs, Tsix and Xist, in mice. Exclusive expression of Tsix from the maternal-X has implicated it as the instrument through which the maternal germline prevents inactivation of the maternal-X in the offspring. Here, we show that Tsix is dispensable for inhibiting Xist and X-inactivation in the early embryo and in cultured stem cells of extra-embryonic lineages. Tsix is instead required to prevent Xist expression as trophectodermal progenitor cells differentiate. Despite induction of wild-type Xist RNA and accumulation of histone H3-K27me3, many Tsix-mutant X-chromosomes fail to undergo ectopic X-inactivation. We propose a novel model of lncRNA function in imprinted X-inactivation that may also apply to other genomically imprinted loci.
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U2 - 10.1038/ncomms5209
DO - 10.1038/ncomms5209
M3 - Article
C2 - 24979243
AN - SCOPUS:84903703837
SN - 2041-1723
VL - 5
JO - Nature communications
JF - Nature communications
M1 - 4209
ER -