Tämä histonidemetylaasi ( di -ja trimetylaasi) pystyy poistamaan kaksi tai kolme metyyliä histoneista H3K79 ja H3K36.
Tämä CXXC2 eli KDM2B pystyy hiljentämään transkriptiota HOXA7 ja MEIS1 geeneistä demetylaatiokyvyillään. Jos tämä CXXC2 poistetaan solusta, metyylien poisto vähenee ,
Jos taas tehdään vakaa poistogeenisyys ja KDM2B vaikutus jää kokonaan pois, irtoaa myös hileentäjä (deasetylaasi) Sirtuiini1 kromatiinilta ( Se on NAD+.sta riippuva) . Silloin histoni H3K79 metyloituu ja histoni H4K16 asetyloituu. ( transkriptio tietysti aktivoituu) Tämä tutkimus assosioi KDM2B (CXXC2):n demetyloivan toiminnan SIRT1- välitteiseen kromatiinin hiljentämiuseen.
FASEB J. 2018 Oct;32(10):5737-5750. doi: 10.1096/fj.201800242R. Epub 2018 May 15.
KDM2B is a histone H3K79 demethylase and induces transcriptional repression via sirtuin-1-mediated chromatin silencing.
Kang JY1, Kim JY1, Kim KB1, Park JW1, Cho H1, Hahm JY1, Chae YC1, Kim D1, Kook H2,3, Rhee S1, Ha NC4, Seo SB1.
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 (CXXC2 ) also known as FBXL10 and a member of the Jumonji C family of proteins (JHDM1B) known for its histone H3K36 demethylase activity, is a di- and trimethyl H3K79 demethylase. We demonstrate that KDM2B induces transcriptional repression of HOXA7 and MEIS1 via 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.
however, demethylase of H3K79 remains unknown despite intensive research.
Here, we show that KDM2B (CXXC2 ) also known as FBXL10 and a member of the Jumonji C family of proteins (JHDM1B) known for its histone H3K36 demethylase activity, is a di- and trimethyl H3K79 demethylase. We demonstrate that KDM2B induces transcriptional repression of HOXA7 and MEIS1 via 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.
KEYWORDS:
H3K79 methylation; SIRT1; histone demethylase; transcription PMID: 29763382 DOI:10.1096/fj.201800242R [Indexed for MEDLINE]
Kommentti: Haen yhteyttä ! CXXC2 ja CXXC8 , Wnt, Sirtuiini , kromatiinin hiljennys" ; Nämä CXXC sinkkisormiset ovat molemmat lysiini metyylitransferaasi 2 lajeja A/B. Joista ei erityisesti mainita vaikutusta Wnt signalointiin pubmed yleiskappaleessa, ehkä siksi että kromatiinin hiljennys vaikutuksessa on mukana sirtuiinitkin ( soluenergiarippuvuus).
Kommenttejani:
H3K79 methylation; SIRT1; histone demethylase; transcription PMID: 29763382 DOI:10.1096/fj.201800242R [Indexed for MEDLINE]
Kommentti: Haen yhteyttä ! CXXC2 ja CXXC8 , Wnt, Sirtuiini , kromatiinin hiljennys" ; Nämä CXXC sinkkisormiset ovat molemmat lysiini metyylitransferaasi 2 lajeja A/B. Joista ei erityisesti mainita vaikutusta Wnt signalointiin pubmed yleiskappaleessa, ehkä siksi että kromatiinin hiljennys vaikutuksessa on mukana sirtuiinitkin ( soluenergiarippuvuus).
KDM2A/B , Wnt signaling
Lu L, Gao Y, Zhang Z, Cao Q, Zhang X, Zou J, Cao Y.
Dev Cell. 2015 Jun 22;33(6):660-74. doi: 10.1016/j.devcel.2015.04.006. Epub 2015 May 21.PMID:
Best matches for Wnt signaling, Sirtuin:
SIRT6 Controls Hematopoietic Stem Cell Homeostasis through Epigenetic Regulation of Wnt Signaling.
Wang H et al. Cell Stem Cell.
(2016)
SIRT1 suppresses adipogenesis by activating Wnt/β-catenin signaling in vivo and in vitro.
Zhou Y et al. Oncotarget.
(2016)
Knockdown
of SIRT7 enhances the osteogenic differentiation of human bone marrow
mesenchymal stem cells partly via activation of the Wnt/β-catenin signaling pathway.
Chen EEM et al. Cell Death Dis.
(2017)
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