Initiation of epigenetic reprogramming of the X chromosome in somatic nuclei transplanted to a mouse oocyte.
The active and inactive X chromosomes have distinct epigenetic marks in somatic nuclei, which undergo reprogramming after transplantation into oocytes. We show that, despite the disappearance of Xist RNA coating in 30 min, the epigenetic memory of the inactive X persists with the precocious appearance of histone H3 trimethylation of lysine 27 (H3-3meK27), without the expected colocalization with Eed/Ezh2. Subsequently, Xist re-appears on the original inactive X, and the silent Xist on the active X undergoes re-activation, resulting in unusual biallelic Xist RNA domains. Despite this abnormal Xist expression pattern, colocalization of H3-3meK27 and Eed is thereafter confined to a single Xist domain, which is presumably on the original inactive X. These epigenetic events differ markedly from the kinetics of preferential paternal X inactivation in normal embryos. All the epigenetic marks on the X are apparently erased in the epiblast, suggesting that the oocyte and epiblast may have distinct properties for stepwise programming of the genome.
Bao
Siqin
S
The Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge.
Miyoshi
Naoki
N
Okamoto
Ikuhiro
I
Jenuwein
Thomas
T
Heard
Edith
E
Azim Surani
M
M
D000483:Alleles; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D019976:Cloning, Organism / Q000379:methods*; D019175:DNA Methylation; D018076:DNA, Complementary / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D020868:Gene Silencing; D006657:Histones / Q000737:chemistry; D017404:In Situ Hybridization, Fluorescence; D007700:Kinetics; D008239:Lysine / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009865:Oocytes / Q000378:metabolism*; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation; D014960:X Chromosome / Q000378:metabolism; D049951:X Chromosome Inactivation
D018076:DNA, Complementary; D006657:Histones; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA; D012313:RNA; D008239:Lysine