Stabilization of Xist RNA mediates initiation of X chromosome inactivation.
The onset of X inactivation is preceded by a marked increase in the level of Xist RNA. Here we demonstrate that increased stability of Xist RNA is the primary determinant of developmental up-regulation. Unstable transcript is produced by both alleles in XX ES cells and in XX embryos prior to the onset of random X inactivation. Following differentiation, transcription of unstable RNA from the active X chromosome allele continues for a period following stabilization and accumulation of transcript on the inactive X allele. We discuss the implications of these findings in terms of models for the initiation of random and imprinted X inactivation.
Sheardown
S A
SA
X Inactivation Group, MRC Clinical Sciences Centre, United Kingdom.
Duthie
S M
SM
Johnston
C M
CM
Newall
A E
AE
Formstone
E J
EJ
Arkell
R M
RM
Nesterova
T B
TB
Alghisi
G C
GC
Rastan
S
S
Brockdorff
N
N
D000483:Alleles; D000818:Animals; D001755:Blastocyst; D002454:Cell Differentiation; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004303:Dosage Compensation, Genetic; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D051379:Mice; D008957:Models, Genetic; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D022661:RNA, Untranslated; D013234:Stem Cells; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000502:physiology
D019384:Nucleic Acid Synthesis Inhibitors; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated; D014157:Transcription Factors; C077885:XIST non-coding RNA; D003609:Dactinomycin