Klug, Maja and Heinz, Sven and Gebhard, Claudia and Schwarzfischer, Lucia and Krause, Stefan W. and Andreesen, Reinhard and Rehli, Michael (2010) Active DNA demethylation in human postmitotic cells correlates with activating histone modifications, but not transcription levels. GENOME BIOLOGY, 11 (6): R63. ISSN 1474-760X,
Full text not available from this repository. (Request a copy)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 time-course 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROMOTER CPG METHYLATION; DENDRITIC CELLS; CHICKEN EMBRYOS; EXCISION-REPAIR; MONOCYTE; GENOME; GLYCOSYLASE; PATTERNS; MAINTENANCE; EXPRESSION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Aug 2020 08:10 |
| Last Modified: | 17 Aug 2020 08:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25461 |
Actions (login required)
 |
View Item |
