Histone macroH2A1.2 relocates to the inactive X chromosome after initiation and propagation of X-inactivation.
The histone macroH2A1.2 has been implicated in X chromosome inactivation on the basis of its accumulation on the inactive X chromosome (Xi) of adult female mammals. We have established the timing of macroH2A1.2 association with the Xi relative to the onset of X-inactivation in differentiating murine embryonic stem (ES) cells using immuno-RNA fluorescence in situ hybridization (FISH). Before X-inactivation we observe a single macroH2A1.2-dense region in both undifferentiated XX and XY ES cells that does not colocalize with X inactive specific transcript (Xist) RNA, and thus appears not to associate with the X chromosome(s). This pattern persists through early stages of differentiation, up to day 7. Then the frequency of XY cells containing a macroH2A1.2-rich domain declines. In contrast, in XX cells there is a striking relocalization of macroH2A1.2 to the Xi. Relocalization occurs in a highly synchronized wave over a 2-d period, indicating a precisely regulated association. The timing of macroH2A1.2 accumulation on the Xi suggests it is not necessary for the initiation or propagation of random X-inactivation.
Mermoud
J E
JE
X-Inactivation Group, Medical Research Council Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, United Kingdom. jmermoud@hgmp.mrc.ac.uk
Costanzi
C
C
Pehrson
J R
JR
Brockdorff
N
N
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D004303:Dosage Compensation, Genetic; D005260:Female; D006657:Histones / Q000378:metabolism*; D008297:Male; D051379:Mice; D012313:RNA / Q000378:metabolism; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012728:Sex Chromatin / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014960:X Chromosome / Q000235:genetics / Q000378:metabolism*; D014998:Y Chromosome / Q000235:genetics
D006657:Histones; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014157:Transcription Factors; C077885:XIST non-coding RNA; C120756:macroH2A histone; D012313:RNA