Letter abstract
Nature Genetics 39, 1390 - 1396 (2007)
Published online: 21 October 2007 | doi:10.1038/ng.2007.5
Evidence that homologous X-chromosome pairing requires transcription and Ctcf protein
Na Xu1,3, Mary E Donohoe1,3, Susana S Silva1,2 & Jeannie T Lee1
X-chromosome inactivation (XCI) ensures the equality of X-chromosome dosages in male and female mammals by silencing one X in the female1. To achieve the mutually exclusive designation of active X (Xa) and inactive X (Xi), the process necessitates that two Xs communicate in trans through homologous pairing2, 3. Pairing depends on a 15-kb region within the genes Tsix and Xite2. Here, we dissect molecular requirements and find that pairing can be recapitulated by 1- to 2-kb subfragments of Tsix or Xite with little sequence similarity. However, a common denominator among them is the presence of the protein Ctcf, a chromatin insulator4, 5, 6, 7 that we find to be essential for pairing. By contrast, the Ctcf-interacting partner, Yy1 (ref. 8), is not required. Pairing also depends on transcription. Transcriptional inhibition prevents new pair formation but does not perturb existing pairs. The kinetics suggest a pairing half-life of <1 h. We propose that pairing requires Ctcf binding and co-transcriptional activity of Tsix and Xite.
- Howard Hughes Medical Institute Department of Molecular Biology, Massachusetts General Hospital Department of Genetics, Harvard Medical School Boston, Massachusetts 02114, USA.
- Gulbenkian PhD Programme in Biomedicine, Rua da Quinta Grande, 6, 2780-156, Oeiras, Portugal.
- These authors contributed equally to this work.
Correspondence to: Jeannie T Lee1 e-mail: lee@molbio.mgh.harvard.edu
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