Unusual chromatin status and organization of the inactive X chromosome in murine trophoblast giant cells.
Mammalian X-chromosome inactivation (XCI) enables dosage compensation between XX females and XY males. It is an essential process and its absence in XX individuals results in early lethality due primarily to extra-embryonic defects. This sensitivity to X-linked gene dosage in extra-embryonic tissues is difficult to reconcile with the reported tendency of escape from XCI in these tissues. The precise transcriptional status of the inactive X chromosome in different lineages has mainly been examined using transgenes or in in vitro differentiated stem cells and the degree to which endogenous X-linked genes are silenced in embryonic and extra-embryonic lineages during early postimplantation stages is unclear. Here we investigate the precise temporal and lineage-specific X-inactivation status of several genes in postimplantation mouse embryos. We find stable gene silencing in most lineages, with significant levels of escape from XCI mainly in one extra-embryonic cell type: trophoblast giant cells (TGCs). To investigate the basis of this epigenetic instability, we examined the chromatin structure and organization of the inactive X chromosome in TGCs obtained from ectoplacental cone explants. We find that the Xist RNA-coated X chromosome has a highly unusual chromatin content in TGCs, presenting both heterochromatic marks such as H3K27me3 and euchromatic marks such as histone H4 acetylation and H3K4 methylation. Strikingly, Xist RNA does not form an overt silent nuclear compartment or Cot1 hole in these cells. This unusual combination of silent and active features is likely to reflect, and might underlie, the partial activity of the X chromosome in TGCs.
Unité de Génétique et Biologie du Développement, Institut Curie, CNRS UMR 3215, INSERM U934, 26 rue d'Ulm, 75248 Paris Cedex 05, France. catherine.corbel@curie.fr
Catherine
C
Corbel
Patricia
P
Diabangouaya
Anne-Valerie
AV
Gendrel
Jennifer C
JC
Chow
Edith
E
Heard
D000107:Acetylation; D000818:Animals; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004622:Embryo, Mammalian / Q000502:physiology*; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D020868:Gene Silencing / Q000502:physiology; D015726:Giant Cells / Q000378:metabolism*; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D014327:Trophoblasts / Q000166:cytology*; D014960:X Chromosome / Q000235:genetics* / Q000378:metabolism; D049951:X Chromosome Inactivation / Q000502:physiology*
D002843:Chromatin