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Changes in chromatin accessibility across the GM-CSF promoter upon T cell activation are dependent on nuclear factor kappaB proteins
journal contribution
posted on 2023-05-16, 16:32 authored by Adele HollowayAdele Holloway, Rao, S, Chen, X, Shannon, MFGranulocyte/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.
History
Publication title
Journal of Experimental MedicineVolume
197Issue
4Pagination
413-423ISSN
0022-1007Department/School
Tasmanian School of MedicinePublisher
Rockefeller University PressPlace of publication
New York, USARepository Status
- Restricted