Preparing the first responders: building the inflammatory transcriptome from the ground up.
In cells of the immune system, inflammatory stimuli trigger highly coordinated cascades of gene activation that are precisely calibrated to the nature and strength of the stimulus. Herein, we describe the forces that control inflammatory gene transcription and highlight that many critical determinants of responsiveness are established prior to challenge. We discuss key steps in the transcription cycle that are regulated during gene activation and the importance of the underlying enhancer landscape. Further, we illustrate how the diversity in regulatory strategies employed at inflammatory genes provides novel opportunities for therapeutic intervention.
Hospital for Special Surgery Research Division and the David Rosensweig Genomics Center, New York, NY 10021, USA; Graduate Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, NY 10021, USA.
Inez
I
Rogatsky
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Electronic address: adelmank@niehs.nih.gov.
Karen
K
Adelman
D002843:Chromatin / Q000235:genetics; D004742:Enhancer Elements, Genetic; D053263:Gene Regulatory Networks; D007113:Immunity, Innate / Q000235:genetics*; D008957:Models, Genetic; D012319:RNA Polymerase II / Q000502:physiology; D059467:Transcriptome
D002843:Chromatin; D012319:RNA Polymerase II