H3K79 dimethylation marks developmental activation of the beta-globin gene but is reduced upon LCR-mediated high-level transcription

作者：Sawado Tomoyuki; Halow Jessica; Im Hogune; Ragoczy Tobias; Bresnick Emery H; Bender M A; Groudine Mark^*

来源：Blood, 2008, 112(2): 406-414.

DOI：10.1182/blood-2007-12-128983

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 pglobin mutant genes during erythroid differentiation. Analysis of fractionated erythroid cells derived from WT/A locus control region (LCR) heterozygous mice reveals no significant H3 K79 dimethylation of the P-globin gene on either allele prior to activation of transcription. Upon transcriptional activation, H3 K79 dimethylation is observed along both WT and ALCR alleles, and both alleles are located in proximity to H3 K79 dimethylation nuclear foci. However, H3 K79 dimethylation is significantly increased along the ALCR allele compared with the WT allele. In addition, analysis of a partial LCR deletion mutant reveals that H3 K79 dimethylation is inversely correlated with P-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 P-globin gene transcription. We propose that H3 K79 dimethylation is destabilized on a highly transcribed template.

• 出版日期2008-7-15