H3 K79 dimethylation marks developmental activation of the beta-globin gene but is reduced upon LCR-mediated high-level transcription.
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.
Sawado
Tomoyuki
T
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Halow
Jessica
J
Im
Hogune
H
Ragoczy
Tobias
T
Bresnick
Emery H
EH
Bender
M A
MA
Groudine
Mark
M
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
D006657:Histones; D005914:Globins