Details

Autor(en) / Beteiligte

• Sun, Sha
• Del Rosario, Brian C.
• Szanto, Attila
• Ogawa, Yuya
• Jeon, Yesu
• Lee, Jeannie T.

Titel

Jpx RNA Activates Xist by Evicting CTCF

Ist Teil von

• Cell, 2013-06, Vol.153 (7), p.1537-1551

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• 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. [Display omitted] [Display omitted] •Jpx RNA is a dosage-sensitive activator of Xist•CTCF binds the Xist promoter and blocks Xist induction•CTCF is an RNA-binding protein and binds Jpx RNA•Jpx activates Xist by evicting CTCF from the Xist promoter The X-linked Jpx noncoding RNA antagonizes the autosomally encoded CTCF transcription factor by titrating it away from the Xist promoter during X chromosome inactivation in mammals, delineating a new mechanism of epigenetic regulation by a noncoding RNA.