Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 286, Issue 51, Pages 44126-44133Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M111.272476
Keywords
-
Categories
Funding
- National Institutes of Health [R01 GM076685]
- Glaxo-SmithKline
Ask authors/readers for more resources
Regulation of TNF gene expression is cell type-and stimulus-specific. We have previously identified highly conserved non-coding 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 II alpha (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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available