title: Deciphering cis-regulatory control in inflammatory cells.
abstract: In innate immune system cells, such as macrophages and dendritic cells, deployment of inducible gene expression programmes in response to microbes and danger signals requires highly precise regulatory mechanisms. The inflammatory response has to be tailored based on both the triggering stimulus and its dose, and it has to be unfolded in a kinetically complex manner that suits the different phases of the inflammatory process. Genomic characterization of regulatory elements in this context indicated that transcriptional regulators involved in macrophage specification act as pioneer transcription factors (TFs) that generate regions of open chromatin that enable the recruitment of TFs activated in response to external inputs. Therefore, competence for responses to a specific stimulus is programmed at an early stage of differentiation by factors involved in lineage commitment and maintenance of cell identity, which are responsible for the organization of a cell-type-specific cis-regulatory repertoire. The basic functional and organizational principles that regulate inflammatory gene expression in professional cells of the innate immune system provide general paradigms on the interplay between differentiation and environmental responses.
authors: Department of Experimental Oncology, European Institute of Oncology (IEO), Via Adamello 16, 20139 Milan, Italy. serena.ghisletti@ieo.eu
authors: Serena
authors: S
authors: Ghisletti
authors: Gioacchino
authors: G
authors: Natoli
mesh_terms: D000107:Acetylation; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D042002:Chromatin Assembly and Disassembly; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics / Q000378:metabolism; D007113:Immunity, Innate; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D006657:Histones; D009707:Nucleosomes; D014157:Transcription Factors
keywords: Pu.1; chromatin; enhancers; epigenome; inflammation; macrophages
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