Identification of a Macrophage-Specific Chromatin Signature in the IL-10 Locus

@article{citeulike:1392505, abstract = {The molecular mechanisms that regulate expression of the immunosuppressive cytokine IL-10 remain poorly understood. In this study, by measuring sensitivity to DNase I digestion, we show that production of IL-10 by primary mouse bone marrow-derived macrophages stimulated through pattern recognition receptors was associated with chromatin remodeling of the IL-10 locus. We also demonstrate that the IL-10 locus is remodeled in primary Th2 cells and IL-10-producing regulatory T cells that have been differentiated in vitro. Strikingly, a novel DNase I-hypersensitive site (HSS-4.5) was identified in stimulated macrophages, but not in T cells. We show that hyperacetylated histones were recruited to this site in stimulated macrophages. Furthermore, HSS-4.5 is highly conserved and contains a putative NF-{kappa}B binding site. In support of a function for this site, NF-{kappa}B p65/RelA was recruited to HSS-4.5 in vivo and its activation was required for optimal IL-10 gene expression in LPS-stimulated macrophages.}, author = {Saraiva{paragraph}, Margarida and Christensen, Jillian R. and Tsytsykova, Alla V. and Goldfeld, Anne E. and Ley, Steven C. and Kioussis, Dimitris and O'Garra, Anne }, citeulike-article-id = {1392505}, journal = {J Immunol}, keywords = {il-10-general}, month = {July}, number = {2}, pages = {1041--1046}, posted-at = {2007-06-15 18:46:42}, priority = {2}, title = {Identification of a Macrophage-Specific Chromatin Signature in the IL-10 Locus}, url = {http://www.jimmunol.org/cgi/content/abstract/175/2/1041}, volume = {175}, year = {2005} }

TY - JOUR ID - citeulike:1392505 L3 - citeulike-article-id:1392505 TI - Identification of a Macrophage-Specific Chromatin Signature in the IL-10 Locus JF - J Immunol VL - 175 IS - 2 SP - 1041 EP - 1046 N2 - The molecular mechanisms that regulate expression of the immunosuppressive cytokine IL-10 remain poorly understood. In this study, by measuring sensitivity to DNase I digestion, we show that production of IL-10 by primary mouse bone marrow-derived macrophages stimulated through pattern recognition receptors was associated with chromatin remodeling of the IL-10 locus. We also demonstrate that the IL-10 locus is remodeled in primary Th2 cells and IL-10-producing regulatory T cells that have been differentiated in vitro. Strikingly, a novel DNase I-hypersensitive site (HSS-4.5) was identified in stimulated macrophages, but not in T cells. We show that hyperacetylated histones were recruited to this site in stimulated macrophages. Furthermore, HSS-4.5 is highly conserved and contains a putative NF-{kappa}B binding site. In support of a function for this site, NF-{kappa}B p65/RelA was recruited to HSS-4.5 in vivo and its activation was required for optimal IL-10 gene expression in LPS-stimulated macrophages. KW - il-10-general AU - Saraiva{paragraph}, Margarida AU - Christensen, Jillian AU - Tsytsykova, Alla AU - Goldfeld, Anne AU - Ley, Steven AU - Kioussis, Dimitris AU - O'Garra, Anne PY - 2005/07/15/ UR - http://www.jimmunol.org/cgi/content/abstract/175/2/1041 ER -