Τίτλος:
Oxidized guanine base lesions function in 8-oxoguanine DNA glycosylase-1-mediated epigenetic regulation of nuclear factor κB-driven gene expression
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
A large percentage of redox-responsive gene promoters contain evolutionarily conserved guanine-rich clusters; guanines are the bases most susceptible to oxidative modification(s). Consequently, 7,8-dihydro-8-oxoguanine (8-oxoG) is one of the most abundant base lesions in promoters and is primarily repaired via the 8-oxoguanine DNA glycosylase-1 (OOG1)-initiated base excision repair pathway. In view of a prompt cellular response to oxidative challenge, we hypothesized that the 8-oxoG lesion and the cognate repair protein OGG1 are utilized in transcriptional gene activation. Here, we document TNFα-induced enrichment of both 8-oxoG and OGG1 in promoters of pro-inflammatory genes, which precedes interaction of NF-κB with its DNA-binding motif. OGG1 bound to 8-oxoG upstream from the NF-κB motif increased its DNA occupancy by promoting an on-rate of both homodimeric and heterodimeric forms of NF-κB. OGG1 depletion decreased both NF-κB binding and gene expression, whereas Nei-like glycosylase-1 and -2 had a marginal effect. These results are the first to document a novel paradigm wherein the DNA repair protein OGG1 bound to its substrate is coupled to DNA occupancy of NF-κB and functions in epigenetic regulation of gene expression. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Συγγραφείς:
Pan, L.
Zhu, B.
Hao, W.
Zeng, X.
Vlahopoulos, S.A.
Hazra, T.K.
Hegde, M.L.
Radak, Z.
Bacsi, A.
Brasier, A.R.
Ba, X.
Boldogh, I.
Περιοδικό:
Journal of Biological Chemistry
Εκδότης:
American Society for Biochemistry and Molecular Biology Inc.
Λέξεις-κλειδιά:
Bins; DNA; Gene expression; Genes; Positive ions; Proteins; Repair, Base excision repairs; Cellular response; DNA repair proteins; Epigenetic regulation; Inflammatory genes; Marginal effects; Nuclear factor kappaB; Oxidative modification, Gene expression regulation, 8 oxoguanine DNA glycosylase 1; CXCL1 chemokine; DNA glycosyltransferase; guanine; immunoglobulin enhancer binding protein; macrophage inflammatory protein 3alpha; tumor necrosis factor; unclassified drug; 8-hydroxyguanine; DNA glycosyltransferase; guanine; immunoglobulin enhancer binding protein; Ogg1 protein, mouse; oxoguanine glycosylase 1, human; tumor necrosis factor, Article; B2M gene; CCL20 gene; controlled study; CXCL1 gene; DNA binding; embryo; epigenetics; gene; gene expression regulation; human; human cell; priority journal; promoter region; protein DNA interaction; protein motif; TNF gene; transcription regulation; analogs and derivatives; animal; biosynthesis; DNA repair; DNA responsive element; genetic epigenesis; genetics; HEK293 cell line; knockout mouse; metabolism; mouse, Animals; DNA Glycosylases; DNA Repair; Epigenesis, Genetic; Gene Expression Regulation, Enzymologic; Guanine; HEK293 Cells; Humans; Mice; Mice, Knockout; NF-kappa B; Response Elements; Tumor Necrosis Factor-alpha
DOI:
10.1074/jbc.M116.751453
