Latent enhancers activated by stimulation in differentiated cells

Renato Ostuni, Viviana Piccolo, Iros Barozzi, Sara Polletti, Alberto Termanini, Silvia Bonifacio, Alessia Curina, Elena Prosperini, Serena Ghisletti, Gioacchino Natoli

Research output: Contribution to journalArticlepeer-review

Abstract

According to current models, once the cell has reached terminal differentiation, the enhancer repertoire is completely established and maintained by cooperatively acting lineage-specific transcription factors (TFs). TFs activated by extracellular stimuli operate within this predetermined repertoire, landing close to where master regulators are constitutively bound. Here, we describe latent enhancers, defined as regions of the genome that in terminally differentiated cells are unbound by TFs and lack the histone marks characteristic of enhancers but acquire these features in response to stimulation. Macrophage stimulation caused sequential binding of stimulus-activated and lineage-determining TFs to these regions, enabling deposition of enhancer marks. Once unveiled, many of these enhancers did not return to a latent state when stimulation ceased; instead, they persisted and mediated a faster and stronger response upon restimulation. We suggest that stimulus-specific expansion of the cis-regulatory repertoire provides an epigenomic memory of the exposure to environmental agents.

Original languageEnglish
Pages (from-to)157-171
Number of pages15
JournalCell
Volume152
Issue number1-2
DOIs
Publication statusPublished - Jan 7 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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