期刊
FEBS LETTERS
卷 590, 期 19, 页码 3407-3415出版社
WILEY-BLACKWELL
DOI: 10.1002/1873-3468.12375
关键词
Hypoxia; INK4A locus; JMJD3
资金
- National Research Foundation of Korea (NRF) [NRF-2013M3A9D3046248, NRF-2012M3A9B6055343]
- National Research Foundation of Korea [2012M3A9B6055343] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Activation of Raf reduces the repressive histone mark H3K27me3 at the INK4a locus by inducing the H3K27me3 demethylase JMJD3. During hypoxia, the catalyitc activity of JMJD3 is reduced due to the limited availability of O-2 as a substrate. In our study, we found that hypoxia prevented Raf-induced JMJD3 from demethylating H3K27me3 at the INK4a locus. Nonetheless, hypoxia did not prevent Raf signaling from inducing INK4a mRNA. Interestingly, we found that hypoxia strongly enhanced the active histone mark H3K4me3 at the INK4a locus by inhibiting the H3K4me3 demethylases JARID1A and JARID1B. Therefore, this study demonstrates that the O-2 concentration in the microenvironment differentially affects the repressive methylation on K27 and the activating methylation on K4 at the INK4a locus by inhibiting the H3K27me3 and H3K4me3 demethylases.
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