Transcriptomics

Dataset Information

3

DNA methylation, H3K4me2, H3K27me3, Pol2 promoter profiling during neuronal differentiation


ABSTRACT: Cellular differentiation entails loss of pluripotency and parallel gain of lineage-specific and ultimately cell-type specific characteristics. Using a murine system that progresses from stem cells to lineage-committed progenitors and further to terminally differentiated neurons we analyzed two repressive epigenetic pathways: DNA methylation and Polycomb-mediated methylation of histone H3 (H3K27me3). We show that several hundred promoters become DNA methylated in lineage-committed progenitor cells. Targets are selected for pluripotency and germline-specific genes, suggesting a role for DNA methylation in stabilizing loss of pluripotency already at the progenitor state. Conversely, we detect loss and acquisition of H3K27me3 at novel targets at both progenitor and terminal state. Surprisingly, many neuron-specific genes that are poised to be activated upon terminal differentiation become Polycomb targets only in progenitor cells. Moreover, promoters marked by H3K27me3 in stem cells frequently become DNA methylated during differentiation, suggesting context-dependent crosstalk between Polycomb and DNA methylation. This data suggest a new model how de novo DNA methylation and dynamic switches in Polycomb targets restrict pluripotency and define the developmental potential of progenitor cells. Keywords: MeDIP-chip, ChIP-chip, neuronal differentiation time-course MeDIP-chip and ChIP-chip experiments were performed with at least two independnet biological replicates. For each condition hybridizations include a dye-swap experiment.

ORGANISM(S): Mus musculus  

SUBMITTER: Fabio Mohn  

PROVIDER: E-GEOD-11489 | ArrayExpress | 2008-06-04

SECONDARY ACCESSION(S): GSE11489PRJNA106419

REPOSITORIES: GEO, ArrayExpress

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Publications

Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors.

Mohn Fabio F   Weber Michael M   Rebhan Michael M   Roloff Tim C TC   Richter Jens J   Stadler Michael B MB   Bibel Miriam M   Schübeler Dirk D  

Molecular cell 20080529 6


Cellular differentiation entails loss of pluripotency and gain of lineage- and cell-type-specific characteristics. Using a murine system that progresses from stem cells to lineage-committed progenitors to terminally differentiated neurons, we analyzed DNA methylation and Polycomb-mediated histone H3 methylation (H3K27me3). We show that several hundred promoters, including pluripotency and germline-specific genes, become DNA methylated in lineage-committed progenitor cells, suggesting that DNA me  ...[more]

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