Hypoxic reprograming of H3K27me3 and H3K4me3 at the INK4A locus

Soojeong Chang, Bongju Park, Kang Choi, Yunwon Moon, Ho Youl Lee, Hyunsung Park

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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 O2 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 O2 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.

Original languageEnglish
Pages (from-to)3407-3415
Number of pages9
JournalFEBS Letters
StatePublished - 1 Oct 2016


  • Hypoxia
  • INK4A locus
  • JMJD3


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