Remodeling of the enhancer landscape during macrophage activation is coupled to enhancer transcription
By M. Kaikkonen, N. Spann, S. Heinz, C. Romanoski, Karmel A. Allison, Joshua D Stender, H. Chun, D. Tough, R. Prinjha, C. Benner and 1 more. Molecules and Cells, 2013
637 citations recorded by the source corpus.
SUMMARY 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 ~3000 enhancer-like regions de novo, enabling visualization of intermediates in enhancer selection and activation. Unexpectedly, we find that enhancer transcription precedes local mono- and di-methylation 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.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/d084d7790b8eb06d0c615175aa28bfd3a86ff675
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Citations in the corpus
- The multidimensional mechanisms of long noncoding RNA function (2017, background): “While some work has shown that the eRNA is dispensable for the deposition of active histone marks at enhancers [91], several other studies have provided abundant proof that eRNAs are functional as RNA species.”
- Trained immunity: a program of innate immune memory in health and disease (2016, background): “One interesting paradigm is provided by latent or de novo enhancers (75, 76), which are genomic regulatory elements that are epigenetically unmarked or marked at low levels in unstimulated cells but gain histone modifications characteristic of enhancers (such as monomethylation of histone H3 at K4, ”