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• W2079156189 abstract "Regulation of TNF gene expression is cell type- and stimulus-specific. We have previously identified highly conserved noncoding regulatory elements within DNase I-hypersensitive sites (HSS) located 9 kb upstream (HSS-9) and 3 kb downstream (HSS+3) of the TNF gene, which play an important role in the transcriptional regulation of TNF in T cells. They act as enhancers and interact with the TNF promoter and with each other, generating a higher order chromatin structure. Here, we report a novel monocyte-specific AT-rich DNase I-hypersensitive element located 7 kb upstream of the TNF gene (HSS-7), which serves as a matrix attachment region in monocytes. We show that HSS-7 associates with topoisomerase IIα (Top2) in vivo and that induction of endogenous TNF mRNA expression is suppressed by etoposide, a Top2 inhibitor. Moreover, Top2 binds to and cleaves HSS-7 in in vitro analysis. Thus, HSS-7, which is selectively accessible in monocytes, can tether the TNF locus to the nuclear matrix via matrix attachment region formation, potentially promoting TNF gene expression by acting as a Top2 substrate." @default.
• W2079156189 created "2016-06-24" @default.
• W2079156189 creator A5027386160 @default.
• W2079156189 creator A5043175989 @default.
• W2079156189 creator A5061083848 @default.
• W2079156189 date "2011-12-01" @default.
• W2079156189 modified "2023-10-07" @default.
• W2079156189 title "Monocyte-specific Accessibility of a Matrix Attachment Region in the Tumor Necrosis Factor Locus" @default.
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• W2079156189 doi "https://doi.org/10.1074/jbc.m111.272476" @default.
• W2079156189 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3243562" @default.
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