Dynamic and Transient Remodeling of the Macrophage IL-10 Promoter during Transcription

@article{citeulike:1373581, abstract = {To gain insight into the molecular mechanism(s) whereby macrophages produce large amounts of IL-10, we analyzed IL-10 gene expression and temporally correlated it with modifications to chromatin associated with the IL-10 promoter. In resting cells, which make essentially no cytokines, the IL-10 promoter is associated with histones containing little or no detectable modifications. Macrophages stimulated in the presence of immune complexes begin to produce high levels of IL-10 pre-mRNA transcripts within minutes of stimulation. Coincident with this transcription was a rapid and dynamic phosphorylation of histone H3 at specific sites in the IL-10 promoter. Histone phosphorylation was closely followed by the binding of transcription factors to the IL-10 promoter. Blocking the activation of ERK prevented histone phosphorylation and transcription factor binding to the IL-10 promoter. In contrast to histone phosphorylation, the peak of histone acetylation at this promoter did not occur until after transcription had peaked. Inhibition of histone deactylase did not alter IL-10 gene expression, suggesting that phosphorylation but not acetylation was the proximal event responsible for IL-10 transcription. Our findings reveal a rapid and well-orchestrated series of events in which ERK activation causes a rapid and transient phosphorylation of histone H3 at specific regions of the IL-10 promoter, resulting in a transient exposure of the IL-10 promoter to the transcription factors that bind there. This exposure is essential for the efficient induction of IL-10 gene expression in macrophages. To our knowledge, this represents a unique way in which the expression of a cytokine gene is regulated in macrophages.}, author = {Zhang, Xia and Edwards, Justin P. and Mosser, David M. }, citeulike-article-id = {1373581}, journal = {J Immunol}, keywords = {erk-il-10}, month = {July}, number = {2}, pages = {1282--1288}, posted-at = {2007-06-08 22:34:22}, priority = {2}, title = {Dynamic and Transient Remodeling of the Macrophage IL-10 Promoter during Transcription}, url = {http://www.jimmunol.org/cgi/content/abstract/177/2/1282}, volume = {177}, year = {2006} }

TY - JOUR ID - citeulike:1373581 L3 - citeulike-article-id:1373581 TI - Dynamic and Transient Remodeling of the Macrophage IL-10 Promoter during Transcription JF - J Immunol VL - 177 IS - 2 SP - 1282 EP - 1288 N2 - To gain insight into the molecular mechanism(s) whereby macrophages produce large amounts of IL-10, we analyzed IL-10 gene expression and temporally correlated it with modifications to chromatin associated with the IL-10 promoter. In resting cells, which make essentially no cytokines, the IL-10 promoter is associated with histones containing little or no detectable modifications. Macrophages stimulated in the presence of immune complexes begin to produce high levels of IL-10 pre-mRNA transcripts within minutes of stimulation. Coincident with this transcription was a rapid and dynamic phosphorylation of histone H3 at specific sites in the IL-10 promoter. Histone phosphorylation was closely followed by the binding of transcription factors to the IL-10 promoter. Blocking the activation of ERK prevented histone phosphorylation and transcription factor binding to the IL-10 promoter. In contrast to histone phosphorylation, the peak of histone acetylation at this promoter did not occur until after transcription had peaked. Inhibition of histone deactylase did not alter IL-10 gene expression, suggesting that phosphorylation but not acetylation was the proximal event responsible for IL-10 transcription. Our findings reveal a rapid and well-orchestrated series of events in which ERK activation causes a rapid and transient phosphorylation of histone H3 at specific regions of the IL-10 promoter, resulting in a transient exposure of the IL-10 promoter to the transcription factors that bind there. This exposure is essential for the efficient induction of IL-10 gene expression in macrophages. To our knowledge, this represents a unique way in which the expression of a cytokine gene is regulated in macrophages. KW - erk-il-10 AU - Zhang, Xia AU - Edwards, Justin AU - Mosser, David PY - 2006/07/15/ UR - http://www.jimmunol.org/cgi/content/abstract/177/2/1282 ER -