| First Author | Li N | Year | 2008 |
| Journal | Proc Natl Acad Sci U S A | Volume | 105 |
| Issue | 44 | Pages | 17055-60 |
| PubMed ID | 18971342 | Mgi Jnum | J:143260 |
| Mgi Id | MGI:3826296 | Doi | 10.1073/pnas.0807765105 |
| Citation | Li N, et al. (2008) Escape from X chromosome inactivation is an intrinsic property of the Jarid1c locus. Proc Natl Acad Sci U S A 105(44):17055-60 |
| abstractText | Although most genes on one X chromosome in mammalian females are silenced by X inactivation, some 'escape' X inactivation and are expressed from both active and inactive Xs. How these escape genes are transcribed from a largely inactivated chromosome is not fully understood, but underlying genomic sequences are likely involved. We developed a transgene approach to ask whether an escape locus is autonomous or is instead influenced by X chromosome location. Two BACs carrying the mouse Jarid1c gene and adjacent X-inactivated transcripts were randomly integrated into mouse XX embryonic stem cells. Four lines with single-copy, X-linked transgenes were identified, and each was inserted into regions that are normally X-inactivated. As expected for genes that are normally subject to X inactivation, transgene transcripts Tspyl2 and Iqsec2 were X-inactivated. However, allelic expression and RNA/DNA FISH indicate that transgenic Jarid1c escapes X inactivation. Therefore, transgenes at 4 different X locations recapitulate endogenous inactive X expression patterns. We conclude that escape from X inactivation is an intrinsic feature of the Jarid1c locus and functionally delimit this escape domain to the 112-kb maximum overlap of the BACs tested. Additionally, although extensive chromatin differences normally distinguish active and inactive loci, unmodified BACs direct proper inactive X expression patterns, establishing that primary DNA sequence alone, in a chromosome position-independent manner, is sufficient to determine X chromosome inactivation status. This transgene approach will enable further dissection of key elements of escape domains and allow rigorous testing of specific genomic sequences on inactive X expression. |
