title: Differentiation-dependent requirement of Tsix long non-coding RNA in imprinted X-chromosome inactivation.
abstract: 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.
authors: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48105, USA.
authors: Emily
authors: E
authors: Maclary
authors: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48105, USA.
authors: Emily
authors: E
authors: Buttigieg
authors: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48105, USA.
authors: Michael
authors: M
authors: Hinten
authors: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48105, USA.
authors: Srimonta
authors: S
authors: Gayen
authors: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48105, USA.
authors: Clair
authors: C
authors: Harris
authors: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48105, USA.
authors: Mrinal Kumar
authors: MK
authors: Sarkar
authors: Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA.
authors: Sonya
authors: S
authors: Purushothaman
authors: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48105, USA.
authors: Sundeep
authors: S
authors: Kalantry
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005260:Female; D018392:Genomic Imprinting; D008297:Male; D051379:Mice / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics*; D049951:X Chromosome Inactivation
chemical_list: D062085:RNA, Long Noncoding; C465658:Tsix transcript, mouse; C077885:XIST non-coding RNA