X-inactivation

To date, the precise mechanisms underlying localization of the long noncoding RNA Xist on the X-chromosome remain poorly understood.


We used our theoretical framework, catRAPID, to investigate Xist interactions with a number of epigenetic modifiers as well as transcription and splicing factors including SUZ12, EZH2, YY1, SAF-A, SFRS1 and SATB. Our calculations suggest that localization and confinement of Xist are finely regulated by multiple factors acting at the interface between chromosome X and the nuclear matrix. Our results are compatible with a model in which following X-chromosome docking mediated by YY1, matrix-associated proteins SAF-A and SATB1 recruit the 5′-half of Xist and drive the translocation in cis of the Xist–PRC2 complex. We also applied our method to SFRS1’s interactome, showing that catRAPID predicts CLIP-seq-binding sites with great accuracy.

 

Agostini, F., Cirillo, D., Bolognesi, B. & Tartaglia, G. G. X-inactivation: quantitative predictions of protein interactions in the Xist network. Nucleic Acids Res. (2012). doi:10.1093/nar/gks968

 

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