First Author | Kaikkonen MU | Year | 2013 |
Journal | Mol Cell | Volume | 51 |
Issue | 3 | Pages | 310-25 |
PubMed ID | 23932714 | Mgi Jnum | J:205969 |
Mgi Id | MGI:5547481 | Doi | 10.1016/j.molcel.2013.07.010 |
Citation | Kaikkonen MU, et al. (2013) Remodeling of the enhancer landscape during macrophage activation is coupled to enhancer transcription. Mol Cell 51(3):310-25 |
abstractText | Recent studies suggest a hierarchical model in which lineage-determining factors act in a collaborative manner to select and prime cell-specific enhancers, thereby enabling signal-dependent transcription factors to bind and function in a cell-type-specific manner. Consistent with this model, TLR4 signaling primarily regulates macrophage gene expression through a pre-existing enhancer landscape. However, TLR4 signaling also induces priming of approximately 3,000 enhancer-like regions de novo, enabling visualization of intermediates in enhancer selection and activation. Unexpectedly, we find that enhancer transcription precedes local mono- and dimethylation of histone H3 lysine 4 (H3K4me1/2). H3K4 methylation at de novo enhancers is primarily dependent on the histone methyltransferases Mll1, Mll2/4, and Mll3 and is significantly reduced by inhibition of RNA polymerase II elongation. Collectively, these findings suggest an essential role of enhancer transcription in H3K4me1/2 deposition at de novo enhancers that is independent of potential functions of the resulting eRNA transcripts. |