2013 Fiscal Year Final Research Report

Analysis of the inhibitory mechanisms of IFN gamma induced gene expression by hypoxia

Research Project

Project/Area Number	22791797
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Functional basic dentistry
Research Institution	Meikai University
Principal Investigator	HIROI Miki 明海大学, 歯学部, 助教 (30419717)
Project Period (FY)	2010-04-01 – 2014-03-31
Keywords	シグナル伝達 / 低酸素 / インターフェロン / ケモカイン / 遺伝子制御
Research Abstract	We have previously shown that hypoxia down-regulated the IFN-induced expression of chemokine CXCL9 and CXCL10 genes in human tumor cell lines. We have explored the mechanisms by which hypoxia down-regulates the IFN-induced gene expressions and found that although HIF-1 was not involved in the transcriptional repression of the IFN-induced genes, recruitments of Pol II, coactivator SRC-1 were inhibited under the hypoxia. In this study, we investigated potential involvements of HIF-2, histone methylation at the promoter region of the CXCL9 genes, and mediator complex that participates in the recruitment of Pol II for the hypoxia-mediated transcriptional repression. Over expression of an active form of HIF-2 in HEK293 cells inhibited the CXCL9 promoter activity, suggesting that HIF-2 negatively regulates CXCL9 expression. Real-time RT-PCR analysis showed that constitutive expressions of mRNAs for methyltransferase and members of mediator complex were observed in HSC-2 cells.

(1 results)