Regulation of cytokine transcription in the contex

Authors: Barbara Nikolajczyk

Publish Date: 2006/10/06

Volume: 54, Issue: 5, Pages: 299-305

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Abstract

Understanding the transcriptional regulation of an important class of innate and adaptive immune system effector molecules the cytokines is increasingly important given the promise cytokine regulation holds for treating various autoimmune and inflammatory diseases Studies defining the mechanisms regulating cytokine transcription initially focused on identifying the cisacting elements and transacting factors that activate cytokine promoters and enhancers In the past these studies were largely completed in the absence of constraints instituted by cellular chromatin Over the past decade it has become obvious that changes in chromatin accessibility critically control rather than simply correlate with the transcriptional activation of most genes including cytokines Hence candidate transcriptional activators are being reevaluated for potency in the context of cellular chromatin Several distinct mechanisms for manipulating the generally repressive context of chromatin have been identified for cytokine genes Most recently single nucleotide polymorphisms in cytokine transcriptional regulatory elements have been shown to play measurable roles in regulating cytokine levels in the context of naturally selected haplotypes Overall subtle differences in DNA sequence and nucleoprotein complex composition including protein posttranslational modification come together in cell typespecific combinations to explain the normal variation in cytokine transcription throughout the human populace

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