The histone H3 lysine 27-specific demethylase Jmjd3 is required for neural commitment.

摘要: Patterns of methylation at lysine 4 and 27 histone H3 have been associated with states gene activation repression that are developmentally regulated thought to underlie the establishment lineage specific expression programs. Recent studies provided fundamental insight into problem specification by comparing global changes in chromatin transcription between ES neural stem (NS) cells, points respectively departure arrival for commitment. With these maps differentiated state place, a central task is now unravel dynamics enables differentiation transitions. In particular, observation lineage-specific genes repressed cells Polycomb-mediated H3-K27 trimethylation (H3-K27me3) demethylated derepressed posited existence demethylase. In order gain epigenetic transitions enable specification, we investigated early stages commitment using as model system monolayer mouse cells. Starting from comprehensive profiling JmjC-domain genes, report here Jmjd3, recently identified H3-K27me3 demethylase, controls key regulators markers neurogenesis required lineage. Our results demonstrate relevance an enzymatic activity antagonizes Polycomb regulation highlight different modalities through which related transcriptional output. By showing demethylase Jmjd3 it resolves bivalent domain Nestin promoter, our work confirms functional resolution had on basis genome-wide correlation their controlled differentiation. addition, data indicate highly gene- context- specific, suggesting interplay methyltransferases demethylases fine-tuning more than on/off alternation states.