Histone code modifications on pluripotential nuclei of reprogrammed somatic cells.
Following hybridization with embryonic stem (ES) cells, somatic genomes are epigenetically reprogrammed and acquire pluripotency. This results in the transcription of somatic genome-derived tissue-specific genes upon differentiation. During nuclear reprogramming, it is expected that DNA and chromatin modifications, believed to function in cell-type-specific epigenotype memory, should be significantly modified. Indeed, current evidence indicates that acetylation and methylation of histone H3 and H4 amino termini play a major role in the regulation of gene activity through the modulation of chromatin conformation. Here, we show that the reprogrammed somatic genome of ES hybrid cells becomes hyperacetylated at H3 and H4, while lysine 4 (K4) of H3 becomes globally hyper-di- and -tri-methylated. In the Oct4 promoter region, histones H3 and H4 are acetylated and H3-K4 is highly tri-methylated on both the ES and reprogrammed somatic genomes, which correlates with gene activation and DNA demethylation. However, H3-K4 is also di- and tri-methylated in the promoter regions of Neurofilament-M (Nfm), Nfl, and Thy-1, which are all silent in both ES and hybrid cells. Thus, H3-K4 di- and tri-methylation of reprogrammed somatic genomes is independent of gene activity and represents one of the major events that occurs during somatic genome reprogramming towards a transcriptional activation-permissive state.
Kimura
Hironobu
H
Department of Development and Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Tada
Masako
M
Nakatsuji
Norio
N
Tada
Takashi
T
D000107:Acetylation; D000818:Animals; D002467:Cell Nucleus / Q000235:genetics*; D002843:Chromatin / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology; D044127:Epigenesis, Genetic; D006657:Histones / Q000096:biosynthesis / Q000235:genetics*; D006822:Hybrid Cells / Q000166:cytology* / Q000648:ultrastructure; D008297:Male; D008745:Methylation; D051379:Mice; D008815:Mice, Inbred Strains; D016900:Neurofilament Proteins / Q000235:genetics; D050814:Octamer Transcription Factor-3; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000648:ultrastructure; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D018800:Thy-1 Antigens / Q000235:genetics; D014157:Transcription Factors; D015533:Transcriptional Activation
D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D016900:Neurofilament Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D018800:Thy-1 Antigens; D014157:Transcription Factors; C061195:neurofilament protein M