Histone acetylation and chromatin conformation are regulated separately at the TNF-α promoter in monocytes and macrophages

Journal of Leukocyte Biology

Kathleen E. Sullivan¹  Nahmah A. Kim¹  Julia Y. Lee¹  Amy Sanford¹ 

[1] Department of Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine Department of Pediatrics, Department of Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine Department of Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine

关键词: gene regulation;    TNF-α;    inflammation;   

DOI  :  10.1189/jlb.1202618

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine, which participates in a wide range of immunoregulatory activities. It is generally produced at highest levels by cells of the myeloid lineage in response to activation of pathogen recognition receptors such as Toll-like receptors. Impaired production predisposes to infection with intracellular organisms, and overproduction results in systemic or organ-specific inflammation. Control of expression is essential to maintain homeostasis, and this control is mediated via multiple strategies. We examined two separate aspects of chromatin accessibility in this study of the human TNF-α promoter. We examined the role of histone acetylation and chromatin remodeling in cell lines and primary cells and identified two individual steps associated with activation of TNF-α production. Histone H3 and H4 acetylation was found to be strongly dependent on the developmental stage of human monocytes. It did not appear to be regulated by acute stimuli, and instead, chromatin remodeling was found to occur after acute stimuli in a cell line competent to produce TNF-α. These data suggest that there is a hierarchy of controls regulating expression of TNF-α. Acetylation of histones is a prerequisite but is insufficient on its own for TNF-α production.

【 授权许可】

Unknown