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Publication : The SNF2H chromatin remodeling enzyme has opposing effects on cytokine gene expression.

First Author  Precht P Year  2010
Journal  Mol Immunol Volume  47
Issue  11-12 Pages  2038-46
PubMed ID  20471682 Mgi Jnum  J:160691
Mgi Id  MGI:4454948 Doi  10.1016/j.molimm.2010.04.009
Citation  Precht P, et al. (2010) The SNF2H chromatin remodeling enzyme has opposing effects on cytokine gene expression. Mol Immunol 47(11-12):2038-46
abstractText  Cytokine gene expression is a key control point in the function of the immune system. Cytokine gene regulation is linked to changes in chromatin structure; however, little is known about the remodeling enzymes mediating these changes. Here we investigated the role of the ATP-dependent chromatin remodeling enzyme SNF2H in mouse T cells; to date, SNF2H has not been investigated in T cells. We found that SNF2H repressed expression of IL-2 and other cytokines in activated cells. By contrast, SNF2H activated expression of IL-3. The ISWI components SNF2H and ACF1 bound to the tested loci, suggesting the regulation was direct. SNF2H decreased accessibility at some binding sites within the IL2 locus, and increased accessibility within some IL3 binding sites. The changes in gene expression positively correlated with accessibility changes, suggesting a simple model that accessibility enables transcription. We also found that loss of the ISWI ATPase SNF2H reduced binding to target genes and protein expression of ACF1, a binding partner for SNF2H, suggesting complex formation stabilized ACF1. Together, these findings reveal a direct role for SNF2H in both repression and activation of cytokine genes.
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