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Evidence that homologous X-chromosome pairing requires transcription and Ctcf protein.
- Source :
-
Nature genetics [Nat Genet] 2007 Nov; Vol. 39 (11), pp. 1390-6. Date of Electronic Publication: 2007 Oct 21. - Publication Year :
- 2007
-
Abstract
- X-chromosome inactivation (XCI) ensures the equality of X-chromosome dosages in male and female mammals by silencing one X in the female. 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 pairing. Pairing depends on a 15-kb region within the genes Tsix and Xite. 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 insulator 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.
- Subjects :
- Animals
Base Sequence
Blastocyst cytology
CCCTC-Binding Factor
Cell Differentiation
DNA metabolism
DNA-Binding Proteins antagonists & inhibitors
DNA-Binding Proteins metabolism
Embryo, Mammalian cytology
Embryo, Mammalian metabolism
Embryonic Stem Cells cytology
Female
Gene Dosage
Humans
In Situ Hybridization, Fluorescence
Male
Mice
Mice, Transgenic
Molecular Sequence Data
Protein Binding
RNA, Long Noncoding
RNA, Small Interfering pharmacology
RNA, Untranslated genetics
RNA, Untranslated metabolism
Repressor Proteins antagonists & inhibitors
Repressor Proteins metabolism
Trans-Activators metabolism
YY1 Transcription Factor genetics
YY1 Transcription Factor metabolism
Zinc Fingers
Chromosomes, Mammalian genetics
DNA-Binding Proteins genetics
Repressor Proteins genetics
Transcription, Genetic
X Chromosome genetics
X Chromosome Inactivation physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1546-1718
- Volume :
- 39
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Nature genetics
- Publication Type :
- Academic Journal
- Accession number :
- 17952071
- Full Text :
- https://doi.org/10.1038/ng.2007.5