Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Jan;136(1):139-46.
doi: 10.1242/dev.026427. Epub 2008 Nov 26.

A proximal conserved repeat in the Xist gene is essential as a genomic element for X-inactivation in mouse

Yuko Hoki  1 , Naomi Kimura, Minako Kanbayashi, Yuko Amakawa, Tatsuya Ohhata, Hiroyuki Sasaki, Takashi Sado
Affiliations

A proximal conserved repeat in the Xist gene is essential as a genomic element for X-inactivation in mouse

Yuko Hoki et al. Development. 2009 Jan.

Abstract

X-inactivation in female mammals is triggered by the association of non-coding Xist RNA in cis with the X chromosome. Although it has been suggested that the A-repeat located in the proximal part of the Xist RNA is required for chromosomal silencing in ES cells, its role in mouse has not yet been addressed. Here, we deleted the A-repeat in mouse and studied its effects on X-inactivation during embryogenesis. The deletion, when paternally transmitted, caused a failure of imprinted X-inactivation in the extraembryonic tissues, demonstrating the essential role of the A-repeat in X-inactivation in the mouse embryo. Unexpectedly, the failure of X-inactivation was caused by a lack of Xist RNA rather than by a defect in the silencing function of the mutated RNA, which we expected to be expressed from the mutated X. Interestingly, the normally silent paternal copy of Tsix, which is an antisense negative regulator of Xist, was ectopically activated in the preimplantation embryo. Furthermore, CpG sites in the promoter region of paternal Xist, which are essentially unmethylated in the extraembryonic tissues of the wild-type female embryo, acquire a significant level of methylation on the mutated paternal X. These findings demonstrate that the DNA sequence deleted on the mutated X, most probably the A-repeat, is essential as a genomic element for the appropriate transcriptional regulation of the Xist/Tsix loci and subsequent X-inactivation in the mouse embryo.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources