Hypoxic reprograming of H3K27me3 and H3K4me3 at the INK 4A locus

Activation of Raf reduces the repressive histone mark H3K27me3 at the INK 4a locus by inducing the H3K27me3 demethylase JMJD 3. During hypoxia, the catalyitc activity of JMJD 3 is reduced due to the limited availability of O 2 as a substrate. In our study, we found that hypoxia prevented Raf‐induced...

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Bibliographic Details
Published inFEBS letters Vol. 590; no. 19; pp. 3407 - 3415
Main Authors Chang, Soojeong, Park, Bongju, Choi, Kang, Moon, Yunwon, Lee, Ho‐Youl, Park, Hyunsung
Format Journal Article
LanguageEnglish
Published 01.10.2016
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Summary:Activation of Raf reduces the repressive histone mark H3K27me3 at the INK 4a locus by inducing the H3K27me3 demethylase JMJD 3. During hypoxia, the catalyitc activity of JMJD 3 is reduced due to the limited availability of O 2 as a substrate. In our study, we found that hypoxia prevented Raf‐induced JMJD 3 from demethylating H3K27me3 at the INK 4a locus. Nonetheless, hypoxia did not prevent Raf signaling from inducing INK 4a mRNA . Interestingly, we found that hypoxia strongly enhanced the active histone mark H3K4me3 at the INK 4a locus by inhibiting the H3K4me3 demethylases JARID 1A and JARID 1B. 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 INK 4a locus by inhibiting the H3K27me3 and H3K4me3 demethylases.
ISSN:0014-5793
1873-3468
DOI:10.1002/1873-3468.12375