Abnormal X: autosome ratio, but normal X chromosome inactivation in human triploid cultures.
BACKGROUND
X chromosome inactivation (XCI) is that aspect of mammalian dosage compensation that brings about equivalence of X-linked gene expression between females and males by inactivating one of the two X chromosomes (Xi) in normal female cells, leaving them with a single active X (Xa) as in male cells. In cells with more than two X's, but a diploid autosomal complement, all X's but one, Xa, are inactivated. This phenomenon is commonly thought to suggest 1) that normal development requires a ratio of one Xa per diploid autosomal set, and 2) that an early event in XCI is the marking of one X to be active, with remaining X's becoming inactivated by default.


RESULTS
Triploids provide a test of these ideas because the ratio of one Xa per diploid autosomal set cannot be achieved, yet this abnormal ratio should not necessarily affect the one-Xa choice mechanism for XCI. Previous studies of XCI patterns in murine triploids support the single-Xa model, but human triploids mostly have two-Xa cells, whether they are XXX or XXY. The XCI patterns we observe in fibroblast cultures from different XXX human triploids suggest that the two-Xa pattern of XCI is selected for, and may have resulted from rare segregation errors or Xi reactivation.


CONCLUSIONS
The initial X inactivation pattern in human triploids, therefore, is likely to resemble the pattern that predominates in murine triploids, i.e., a single Xa, with the remaining X's inactive. Furthermore, our studies of XIST RNA accumulation and promoter methylation suggest that the basic features of XCI are normal in triploids despite the abnormal X:autosome ratio.
Gartler
Stanley M
SM
Department of Medicine, Division of Medical Genetics,, University of Washington, Seattle, WA 98195, USA. gartler@genetics.washington.edu
Varadarajan
Kartik R
KR
Luo
Ping
P
Norwood
Thomas H
TH
Canfield
Theresa K
TK
Hansen
R Scott
RS
D002478:Cells, Cultured; D002877:Chromosomes, Human; D041321:Chromosomes, Human, X; D002999:Clone Cells; D019175:DNA Methylation; D004276:DNA, Satellite / Q000032:analysis; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D008297:Male; D011123:Polyploidy; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000032:analysis; D049951:X Chromosome Inactivation
D004276:DNA, Satellite; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA