کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5526889 1401554 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
SIRT6 regulated nucleosomal occupancy affects Hexokinase 2 expression
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
SIRT6 regulated nucleosomal occupancy affects Hexokinase 2 expression
چکیده انگلیسی


- IL-1β mediates open chromatin conformation around HK2 promoter.
- SIRT6 abrogates HK2 expression by causing chromatin compaction around MZF1 sites.
- IL-1β induced HIF-1α prevents MZF1-SIRT6 complex binding at MZF1 binding sites.

To understand the molecular association between inflammation and dysregulated metabolism in glioblastoma, the effect of IL-1β on Hexokinase 2 (HK2) expression was investigated. IL-1β induced HK2 expression was accompanied by heightened SIRT6 and MZF1 levels. IL-1β mediated overall decrease in chromatin compactness on HK2 promoter involved diminished nucleosomal occupancy around the most labile region bearing MZF1 sites. Importantly, SIRT6 and MZF1 served as negative regulators of HK2. Ectopic SIRT6 induced formation and recruitment of MZF1-SIRT6 complex to MZF1 site was concomitant with increased nucleosomal occupancy. The function of SIRT6 as co-repressor of MZF1 was inconspicuous in cells treated with IL-1β alone, as IL-1β-induced HIF-1α prevented SIRT6 availability for interaction with MZF1. Taken together, SIRT6 over-expression establishes a condition whereby reconfiguration of the HK2 promoter chromatin structure makes it receptive to interaction with MZF1/SIRT6 complex, thereby favouring a regulatory state conducive to diminished transcription.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 357, Issue 1, 1 August 2017, Pages 98-106
نویسندگان
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