The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha (Cell, 2010, 140:280-293)

報告日期: 2010/04/20
報告時間: 16:00/16:50
報告學生: 鄭昭旻
講評老師: 洪建中

The Histone Deacetylase Sirt6 Regulates Glucose Homeostasis via Hif1a

Lei Zhong, Agustina D’Urso, Agustina D’Urso, et al. Cell 140, 280–293, January 22, 2010


Speaker: Chao-Min, Cheng

Commentator: Jan-Jong, Hong

Date/Time: 2010/04/20 16:00-16:50



   Hypoglycemia is the major phenotype in SIRT6-deficient mice, and SIRT6-deficient mice almost die early in life. SIRT6 is a mammalian homolog to yeast Sir2 (silencing factor 2), and SIRT6 acts as a histone deacetylase specifically at histone H3 lycine 9. So far, the correlation between SIRT6 and glucose metabolism is still unclear. In this study, the authors used 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and flow-cytometry to verify which tissues had increased glucose uptake and whether SIRT6 affects glucose uptake in a cell-autonomous fashion, respectively. From the result of CHIP assay and real-time RT-PCR, they validated that SIRT6 represses the critical glycolytic genes expression by binding and deacetylating at their promoter. Furthermore, the authors confirmed that SIRT6 can interact with hypoxia inducible factor 1(Hif1a) by coIP and polysome profiling analysis. Hif1a protein synthesis and stability both increase in SIRT6 KO cells. The HRE (Hif1a response element) luciferase assay and flow-cytometry indicate that SIRT6 plays a very important role in regulating Hif1a-dependent glucose pathway. Thus, from the above-mentioned data, they concluded that SIRT6 functions as a corepresser of Hif1a for modulating multiple glycolytic genes in glucose metabolism under normal nutrient condition.



1.    Mostoslavsky, R., Chua, K.F., Lombard, D.B., Pang, W.W., Fischer, M.R., Gellon, L., Liu, P., Mostoslavsky, G., Franco, S., Murphy, M.M., et al. (2006). Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124, 315–329.

2.    Zimmer, M., Ebert, B.L., Neil, C., Brenner, K., Papaioannou, I., Melas, A., Tolliday, N., Lamb, J., Pantopoulos, K., Golub, T., et al. (2008). Small-molecule inhibitors of HIF-2a translation link its 50UTR iron-responsive element to oxygen sensing. Mol. Cell 32, 838–848.