Changes in chromatin accessibility across the GM-CSF promoter upon T cell activation are dependent on nuclear factor kappaB proteins.

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)-kappaB activation. To investigate the relationship between NF-kappaB 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-kappaB 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-kappaB 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-kappaB-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-kappaB proteins binding to the CD28 response region of the promoter.

• Authors: Adele F Holloway, Sudha Rao, Xinxin Chen, M Frances Shannon
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 197 Issue 4 Pg. 413-23 (Feb 17 2003) ISSN: 0022-1007 [Print] United States
• PMID: 12591900 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD28 Antigens
• Chromatin
• NF-kappa B
• Nuclear Proteins
• Nucleosomes
• RNA, Messenger
• Transcription Factors
• Granulocyte-Macrophage Colony-Stimulating Factor
• SMARCA4 protein, human
• DNA Helicases

Topics

• CD28 Antigens
• Chromatin (metabolism)
• DNA Helicases
• Granulocyte-Macrophage Colony-Stimulating Factor (genetics)
• Humans
• Jurkat Cells
• NF-kappa B (metabolism)
• Nuclear Proteins (physiology)
• Nucleosomes (metabolism)
• Promoter Regions, Genetic
• RNA, Messenger (analysis)
• Response Elements
• T-Lymphocytes (immunology)
• Transcription Factors (physiology)