Dynamic regulation of histone H3 methylated at lysine 79 within a tissue-specific chromatin domain

被引:55
作者
Im, H
Park, C
Feng, Q
Johnson, KD
Kiekhaefer, CM
Choi, K
Zhang, Y
Bresnick, EH
机构
[1] Univ Wisconsin, Sch Med, Dept Pharmacol, Mol & Cellular Pharmacol Program, Madison, WI 53706 USA
[2] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Dev Biol Program, St Louis, MO 63110 USA
[4] Univ N Carolina, Dept Biochem & Biophys, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
关键词
D O I
10.1074/jbc.M300890200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Post-translational modifications of individual lysine residues of core histones can exert unique functional consequences. For example, methylation of histone H3 at lysine 79 (H3-meK79) has been implicated recently in gene silencing in Saccharomyces cerevisiae. However, the distribution and function of H3-meK79 in mammalian chromatin are not known. We found that H3-meK79 has a variable distribution within the murine beta-globin locus in adult erythroid cells, being preferentially enriched at the active betamajor gene. By contrast, acetylated H3 and H4 and H3 methylated at lysine 4 were enriched both at betamajor and at the upstream locus control region. H3-meK79 was also enriched at the active cad gene, whereas the transcriptionally inactive loci necdin and MyoD1 contained very little H3-meK79. As the pattern of H3-meK79 at the beta-globin locus differed between adult and embryonic erythroid cells, establishment and/or maintenance of H3-meK79 was developmentally dynamic. Genetic complementation analysis in null cells lacking the erythroid and megakaryocyte-specific transcription factor p45/NF-E2 showed that p45/NF-E2 preferentially establishes H3-meK79 at the betamajor promoter. These results support a model in which H3-meK79 is strongly enriched in mammalian chromatin at active genes but not uniformly throughout active chromatin domains. As H3-meK79 is highly regulated at the beta-globin locus, we propose that the murine ortholog of Disruptor of Telomeric Silencing-1-like (mDOT1L) methyltransferase, which synthesizes H3-meK79, regulates beta-globin transcription.
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收藏
页码:18346 / 18352
页数:7
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