Premium
Hypoxic reprograming of H3K27me3 and H3K4me3 at the INK 4A locus
Author(s) -
Chang Soojeong,
Park Bongju,
Choi Kang,
Moon Yunwon,
Lee HoYoul,
Park Hyunsung
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12375
Subject(s) - h3k4me3 , demethylase , locus (genetics) , histone , histone methylation , biology , chemistry , cancer research , microbiology and biotechnology , genetics , dna methylation , gene , gene expression , promoter
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.