Affiliation:
1. Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, ACT 2601, Australia
Abstract
Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a key cytokine in myelopoiesis and aberrant expression is associated with chronic inflammatory disease and myeloid leukemias. This aberrant expression is often associated with constitutive nuclear factor (NF)-κB activation. To investigate the relationship between NF-κB and GM-CSF transcription in a chromatin context, we analyzed the chromatin structure of the GM-CSF gene in T cells and the role of NF-κB proteins in chromatin remodeling. We show here that chromatin remodeling occurs across a region of the GM-CSF gene between −174 and +24 upon T cell activation, suggesting that remodeling is limited to a single nucleosome encompassing the proximal promoter. Nuclear NF-κB levels appear to play a critical role in this process. In addition, using an immobilized template assay we found that the ATPase component of the SWI/SNF chromatin remodeling complex, brg1, is recruited to the GM-CSF proximal promoter in an NF-κB–dependent manner in vitro. These results suggest that chromatin remodeling across the GM-CSF promoter in T cells is a result of recruitment of SWI/SNF type remodeling complexes by NF-κB proteins binding to the CD28 response region of the promoter.
Publisher
Rockefeller University Press
Subject
Immunology,Immunology and Allergy
Cited by
64 articles.
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