Polycomb proteins targeted by a short repeat RNA to the mouse X-chromosome

By J. Zhao, Bryan K. Sun, Jennifer A. Erwin, Ji‐Joon Song, Jeannie T. Lee. Science, 2008

1,636 citations recorded by the source corpus.

To equalize X-chromosome dosages between the sexes, the female mammal inactivates one of her two X chromosomes. X-chromosome inactivation (XCI) is initiated by expression of Xist, a 17-kb noncoding RNA (ncRNA) that accumulates on the X in cis. Because interacting factors have not been isolated, the mechanism by which Xist induces silencing remains unknown. We discovered a 1.6-kilobase ncRNA (RepA) within Xist and identified the Polycomb complex, PRC2, as its direct target. PRC2 is initially recruited to the X by RepA RNA, with Ezh2 serving as the RNA binding subunit. The antisense Tsix RNA inhibits this interaction. RepA depletion abolishes full-length Xist induction and trimethylation on lysine 27 of histone H3 of the X. Likewise, PRC2 deficiency compromises Xist up-regulation. Therefore, RepA, together with PRC2, is required for the initiation and spread of XCI. We conclude that a ncRNA cofactor recruits Polycomb complexes to their target locus.

Subfields: Cancer Research, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ce01df306aeeeb4ea34a3b04ab04111e14f05928

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Citations in the corpus

Epigenetics and gene expression (2010, background): “(PRC2 possesses methyltransferase activity and trimethylates H3K27).”
Long non-coding RNAs: insights into functions (2009, background): “A small internal non-coding transcript from the Xist locus, RepA , recruits PRC2 to silence one X chromosom”
Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15INK4B tumor suppressor gene (2010, background): “The other ncRNA, Xist, directly associates with EZH2 through RepA, a motif comprising 7.5 tandem repeats of a 28-nucleotide sequence that folds into two conserved stem-loop structures (Wutz et al., 2002; Zhao et al., 2008).”
Long noncoding RNAs: functional surprises from the RNA world. (2009, background): “Ezh2 (Enhancer of zeste homolog 2), a histone methyltransferase and member of Polycomb-repressive complex 2 (PRC2), was found to directly bind a 1.6-kb-long ncRNA known as RepA (Zhao et al. 2008).”
Occupying chromatin: Polycomb mechanisms for getting to genomic targets, stopping transcriptional traffic, and staying put (2013, background): “Portions of the large Xist RNA, particularly its A repeat region (RepA), have been implicated in PRC2 recruitment (Plath et al., 2003; Zhao et al., 2008).”