BioProject

According to current models, transcription factors (TFs) activated by extracellular stimuli operate in the context of a pre-established enhancer repertoire induced and maintained by lineage-specific TFs. More...

According to current models, transcription factors (TFs) activated by extracellular stimuli operate in the context of a pre-established enhancer repertoire induced and maintained by lineage-specific TFs. Here, we uncovered the existence of latent enhancers, defined as regions of the genome that in terminally differentiated cells are poorly accessible and lack the histone marks characteristic of enhancers, but readily acquire these features in response to extracellular cues. Stimulation of resting macrophages caused simultaneous binding of stimulus-activated TFs and lineage-determining TFs to these regions, enabling deposition of enhancer-specific features. Once unveiled, these enhancers did not return to a latent state even when stimulation ceased; instead, they persisted and mediated a faster and stronger response upon restimulation. We suggest that stimulus-specific expansion of the available cis-regulatory repertoire provides an epigenomic memory of the exposure to environmental agents. Overall design: Poly(A) fraction of the total mRNA of resting and stimulated murine bone marrow derived macrophages was extracted and subjected to by multiparallel sequencing. Experiments carried out in untreated cells as well as in cells treated for 4hrs (IFNg, IL4, TNFa, TGFb1, IL1b, MALP2, CpG) Less...