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Báo cáo y học: "Active DNA demethylation in human postmitotic cells correlates with activating histone modifications, but not transcription levels"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: Active DNA demethylation in human postmitotic cells correlates with activating histone modifications, but not transcription levels. | Klug et al. Genome Biology 2010 11 R63 http genomebiology.eom 2010 11 6 R63 w Genome Biology RESEARCH _ Open Access Active DNA demethylation in human postmitotic cells correlates with activating histone modifications but not transcription levels Maja Klug 1 Sven Heinz2 Claudia Gebhard1 Lucia Schwarzfischer1 Stefan W Krause3 Reinhard Andreesen1 and Michael Rehli 1 Abstract Background In mammals the dynamics of DNA methylation in particular the regulated active removal of cytosine methylation has remained a mystery partly due to the lack of appropriate model systems to study DNA demethylation. Previous work has largely focused on proliferating cell types that are mitotically arrested using pharmacological inhibitors to distinguish between active and passive mechanisms of DNA demethylation. Results We explored this epigenetic phenomenon in a natural setting of post-mitotic cells the differentiation of human peripheral blood monocytes into macrophages or dendritic cells which proceeds without cell division. Using a global comparative CpG methylation profiling approach we identified many novel examples of active DNA demethylation and characterized accompanying transcriptional and epigenetic events at these sites during monocytic differentiation. We show that active DNA demethylation is not restricted to proximal promoters and that the timecourse of demethylation varies for individual CpGs. Irrespective of their location the removal of methylated cytosines always coincided with the appearance of activating histone marks. Conclusions Demethylation events are highly reproducible in monocyte-derived dendritic cells from different individuals. Our data suggest that active DNA demethylation is a precisely targeted event that parallels or follows the modification of histones but is not necessarily coupled to alterations in transcriptional activity. Background The methylation of cytosine in the context of CpG dinucleotides in mammalian DNA is generally associated with gene .