title: Jpx RNA activates Xist by evicting CTCF.
abstract: In mammals, dosage compensation between XX and XY individuals occurs through X chromosome inactivation (XCI). The noncoding Xist RNA is expressed and initiates XCI only when more than one X chromosome is present. Current models invoke a dependency on the X-to-autosome ratio (X:A), but molecular factors remain poorly defined. Here, we demonstrate that molecular titration between an X-encoded RNA and an autosomally encoded protein dictates Xist induction. In pre-XCI cells, CTCF protein represses Xist transcription. At the onset of XCI, Jpx RNA is upregulated, binds CTCF, and extricates CTCF from one Xist allele. We demonstrate that CTCF is an RNA-binding protein and is titrated away from the Xist promoter by Jpx RNA. Thus, Jpx activates Xist by evicting CTCF. The functional antagonism via molecular titration reveals a role for long noncoding RNA in epigenetic regulation.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Sha
authors.initials: S
authors.lastname: Sun
authors.forename: Brian C
authors.initials: BC
authors.lastname: Del Rosario
authors.forename: Attila
authors.initials: A
authors.lastname: Szanto
authors.forename: Yuya
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Yesu
authors.initials: Y
authors.lastname: Jeon
authors.forename: Jeannie T
authors.initials: JT
authors.lastname: Lee
mesh_terms: D000818:Animals; D000076246:CCCTC-Binding Factor; D033481:Chromosomes, Mammalian / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015854:Up-Regulation; D014960:X Chromosome / Q000378:metabolism; D049951:X Chromosome Inactivation
chemical_list: D000076246:CCCTC-Binding Factor; C000619698:Ctcf protein, mouse; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; C465658:Tsix transcript, mouse; C077885:XIST non-coding RNA