title: H3 K79 dimethylation marks developmental activation of the beta-globin gene but is reduced upon LCR-mediated high-level transcription.
abstract: Genome-wide analyses of the relationship between H3 K79 dimethylation and transcription have revealed contradictory results. To clarify this relationship at a single locus, we analyzed expression and H3 K79 modification levels of wild-type (WT) and transcriptionally impaired beta-globin mutant genes during erythroid differentiation. Analysis of fractionated erythroid cells derived from WT/Delta locus control region (LCR) heterozygous mice reveals no significant H3 K79 dimethylation of the beta-globin gene on either allele prior to activation of transcription. Upon transcriptional activation, H3 K79 di-methylation is observed along both WT and DeltaLCR alleles, and both alleles are located in proximity to H3 K79 dimethylation nuclear foci. However, H3 K79 di-methylation is significantly increased along the DeltaLCR allele compared with the WT allele. In addition, analysis of a partial LCR deletion mutant reveals that H3 K79 dimethylation is inversely correlated with beta-globin gene expression levels. Thus, while our results support a link between H3 K79 dimethylation and gene expression, high levels of this mark are not essential for high level beta-globin gene transcription. We propose that H3 K79 dimethylation is destabilized on a highly transcribed template.
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Sawado
authors.forename: Jessica
authors.initials: J
authors.lastname: Halow
authors.forename: Hogune
authors.initials: H
authors.lastname: Im
authors.forename: Tobias
authors.initials: T
authors.lastname: Ragoczy
authors.forename: Emery H
authors.initials: EH
authors.lastname: Bresnick
authors.forename: M A
authors.initials: MA
authors.lastname: Bender
authors.forename: Mark
authors.initials: M
authors.lastname: Groudine
mesh_terms: D000818:Animals; D023281:Genomics / Q000379:methods; D005914:Globins / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000196:embryology; D019901:Locus Control Region / Q000235:genetics*; D008745:Methylation; D051379:Mice; D008817:Mice, Mutant Strains; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D006657:Histones; D005914:Globins