Transient homologous chromosome pairing marks the onset of X inactivation.
Mammalian X inactivation turns off one female X chromosome to enact dosage compensation between XX and XY individuals. X inactivation is known to be regulated in cis by Xite, Tsix, and Xist, but in principle the two Xs must also be regulated in trans to ensure mutually exclusive silencing. Here, we demonstrate that interchromosomal pairing mediates this communication. Pairing occurs transiently at the onset of X inactivation and is specific to the X-inactivation center. Deleting Xite and Tsix perturbs pairing and counting/choice, whereas their autosomal insertion induces de novo X-autosome pairing. Ectopic X-autosome interactions inhibit endogenous X-X pairing and block the initiation of X-chromosome inactivation. Thus, Tsix and Xite function both in cis and in trans. We propose that Tsix and Xite regulate counting and mutually exclusive choice through X-X pairing.
Xu
Na
N
Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School Boston, MA 02114, USA.
Tsai
Chia-Lun
CL
Lee
Jeannie T
JT
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D023902:Chromosome Pairing; D005260:Female; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D009154:Mutation; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D013234:Stem Cells; D019076:Transgenes; D014960:X Chromosome / Q000235:genetics / Q000502:physiology*; D049951:X Chromosome Inactivation
D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C465658:Tsix transcript, mouse; C077885:XIST non-coding RNA