In:
Blood, American Society of Hematology, Vol. 105, No. 2 ( 2005-01-15), p. 711-720
Abstract:
Interleukin-12 receptor β1 (IL12RB1) is expressed on a variety of immune cells, including T and natural killer (NK) cells and macrophages, and is involved in innate and adaptive immune responses. Levels of IL12RB1 mRNA are dynamically regulated by various cytokines, including interferon-γ (IFN-γ) and IL-15. To reveal the regulatory mechanisms governing IL12RB1 gene expression, we analyzed the transcriptional regulatory region of the mouse IL12RB1 gene. Promoter analyses in a mouse macrophage cell line, RAW264.7, revealed that the 2508-bp region upstream of the transcriptional start site is sufficient for the full transcriptional activation of the IL12RB1 gene by IFN-γ or IL-15. Analyses of the deletion mutants revealed critical roles of IRE/ISRE and ETS/PU.1 elements, to which IRF3 and PU.1, respectively, bound. Notably, chromatin immunoprecipitation (ChIP) assays revealed IL-15 rapidly induced histone H3 acetylation at the IL12RB1 promoter. Consistently, IL-15, as a histone deacetylase inhibitor, synergistically enhanced IL12RB1 gene expression and promoter activation by IFN-γ through increased protein binding to ETS/PU.1 and IRE/ISRE sites. Additionally, IL12RB1 promoter activation by IFN-γ was enhanced by the coexpression of a coactivator protein, CBP. Thus, IL-15 induces chromatin remodeling of the IL12RB1 gene promoter, increasing IL12RB1 mRNA expression in synergy with IFN-γ through the recruitment of PU.1 and IRF3.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood-2004-03-0842
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2005
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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