KDM2B is a histone H3K79 demethylase and induces transcriptional repression via sirtuin-1-mediated chromatin silencingopen access
- Authors
- Kang, Joo-Young; Kim, Ji-Young; Kim, Kee-Beom; Park, Jin Woo; Cho, Hana; Hahm, Ja Young; Chae, Yun-Cheol; Kim, Daehwan; Kook, Hyun; Rhee, Sangmyeong; Ha, Nam-Chul; Seo, Sang-Beom
- Issue Date
- Oct-2018
- Publisher
- FEDERATION AMER SOC EXP BIOL
- Keywords
- histone demethylase; H3K79 methylation; SIRT1; transcription
- Citation
- FASEB JOURNAL, v.32, no.10, pp 5737 - 5750
- Pages
- 14
- Journal Title
- FASEB JOURNAL
- Volume
- 32
- Number
- 10
- Start Page
- 5737
- End Page
- 5750
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/740
- DOI
- 10.1096/fj.201800242R
- ISSN
- 0892-6638
1530-6860
- Abstract
- The methylation of histone H3 lysine 79 (H3K79) is an active chromatin marker and is prominent in actively transcribed regions of the genome; however, demethylase of H3K79 remains unknown despite intensive research. Here, we show that KDM2B, also known as FBXL10 and a member of the Jumonji C family of proteins known for its histone H3K36 demethylase activity, is a di- and trimethyl H3K79 demethylase. We demonstrate that KDM2B induces transcriptional repression of HOXA7 and MEIS1via occupancy of promoters and demethylation of H3K79. Furthermore, genome-wide analysis suggests that H3K79 methylation levels increase when KDM2B is depleted, which indicates that KDM2B functions as an H3K79 demethylase in vivo. Finally, stable KDM2B-knockdown cell lines exhibit displacement of NAD(+)-dependent deacetylase sirtuin-1 (SIRT1) from chromatin, with concomitant increases in H3K79 methylation and H4K16 acetylation. Our findings identify KDM2B as an H3K79 demethylase and link its function to transcriptional repression via SIRT1-mediated chromatin silencing.Kang, J.-Y., Kim, J.-Y., Kim, K.-B., Park, J. W., Cho, H., Hahm, J. Y., Chae, Y.-C., Kim, D., Kook, H., Rhee, S., Ha, N.-C., Seo, S.-B. KDM2B is a histone H3K79 demethylase and induces transcriptional repression via sirtuin-1-mediated chromatin silencing.
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