Early loss of Xist RNA expression and inactive X chromosome associated chromatin modification in developing primordial germ cells.
BACKGROUND
The inactive X chromosome characteristic of female somatic lineages is reactivated during development of the female germ cell lineage. In mouse, analysis of protein products of X-linked genes and/or transgenes located on the X chromosome has indicated that reactivation occurs after primordial germ cells reach the genital ridges.


RESULTS
We present evidence that the epigenetic reprogramming of the inactive X-chromosome is initiated earlier than was previously thought, around the time that primordial germ cells (PGCs) migrate through the hindgut. Specifically, we find that Xist RNA expression, the primary signal for establishment of chromosome silencing, is extinguished in migrating PGCs. This is accompanied by displacement of Polycomb-group repressor proteins Eed and Suz(12), and loss of the inactive X associated histone modification, methylation of histone H3 lysine 27.


CONCLUSIONS
We conclude that X reactivation in primordial germ cells occurs progressively, initiated by extinction of Xist RNA around the time that germ cells migrate through the hindgut to the genital ridges. The events that we observe are reminiscent of X reactivation of the paternal X chromosome in inner cell mass cells of mouse pre-implantation embryos and suggest a unified model in which execution of the pluripotency program represses Xist RNA thereby triggering progressive reversal of epigenetic silencing of the X chromosome.
de Napoles
Mariana
M
Medical Research Council Clinical Sciences Centre, Imperial College Faculty of Medicine, Hammersmith Hospital, London, United Kingdom.
Nesterova
Tatyana
T
Brockdorff
Neil
N
D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D005854:Germ Cells / Q000378:metabolism*; D017404:In Situ Hybridization, Fluorescence; D008239:Lysine / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012313:RNA / Q000235:genetics*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D019076:Transgenes; D014960:X Chromosome; D049951:X Chromosome Inactivation
D002843:Chromatin; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA; D012313:RNA; D008239:Lysine