组蛋白去甲基化酶JMJD3研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2017-0148

摘要/Abstract

摘要：

组蛋白甲基化状态是有不同类型的甲基转移酶和去甲基化酶来控制的。H3K27me2/3可以由多梳家族蛋白（如甲基转移酶EZH2）控制形成,其去甲基化后可以催化基因表达。目前共鉴定出JMJD3和UTX两种H3K27me3的去甲基化酶。大量研究发现,JMJD3可以促进细胞分化和衰老,参与调控肿瘤发生与发展。综述了JMJD3在胚胎发育及肿瘤发生、发展中的作用及其调节机制,并对其在肿瘤诊断和治疗方面的应用前景进行展望,旨为今后的研究工作奠定理论基础。

关键词: JMJD3, H3K27me3, 胚胎发育, 细胞衰老, 肿瘤发生

Abstract:

Histone methylation state is dynamically regulated by different groups of histone methyltransferases and demethylases. H3K27me2/3 is controlled by the polycomb group proteins（such as methyltransferase EZH2）,and its demethylation can activate gene expression. At present,two H3K27me3 demethylation enzymes,JMJD3 and UTX,have been identified. Moreover,a large number of studies have found that JMJD3 may promote cell differentiation and aging,and involve in the regulation of the occurrence and development of tumor. Here we summarize the roles and regulation mechanisms of JMJD3 in embryonic development as well as the occurrence and development of tumor,and the broad prospects in tumor diagnosis and treatment,for laying a theoretical basis for the future research work.

Key words: JMJD3, H3K27me3, embryonic development, cell aging, tumorigenesis

胡姗,韩聪,胡建宏,朱海鲸. 组蛋白去甲基化酶JMJD3研究进展[J]. 生物技术通报, 2017, 33(9): 64-72.

HU Shan,HAN Cong,HU Jian-hong,ZHU Hai-jing. Research Progress on Histone Demethylase JMJD3[J]. Biotechnology Bulletin, 2017, 33(9): 64-72.

参考文献

[1] Xiang Y, Zhu Z, Han G, et al. JMJD3 is a histone H3K27 demethylase[J] . Cell Res, 2007, 17（10）：850-857.
[2] Li Q, Wang HY, Chepelev I, et al. Stage-dependent and locus-specific role of histone demethylase Jumonji D3（JMJD3）in the embryonic stages of lung development[J] . PLoS One, 2014, 10（7）：e1004524.
[3] Zhao L, Zhang Y, Gao Y, et al. JMJD3 promotes SAHF formation in senescent WI38 cells by triggering an interplay between demethylation and phosphorylation of RB protein[J] . Cell Death Differ, 2015, 22（10）：1630-1640.
[4] Burchfield JS, Li Q, Wang HY, Wang RF. JMJD3 as an epigenetic regulator in development and disease[J] . Int J Biochem Cell Biol, 2015, 67：148-157.
[5] Shi Y, Lan F, et al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1[J] . Cell, 2004, 119（7）：941-953.
[6] Peters AH, KubicekS, Mechtler K, et al. Partitioning and plasticity of repressive histone methylation states in mammalian chromatin[J] . Molecular Cell, 2003, 12：1577-1589.
[7] Barski A, Cuddapah S, Cui K, et al. High-resolution profiling of histone methylations in the human genome[J] . Cell, 2007, 129：823-837.
[8] Klose RJ, Kallin EM, Zhang Y. JmjC-domain-containing proteins and histone demethylation[J] . Nat Rev Genet, 2006, 7（9）：715-727.
[9] Ke XS, Qu Y, Rostad K, et al. Genome-wide profiling of histone h3 lysine 4 and lysine 27 trimethylation reveals an epigenetic signature in prostate carcinogenesis[J] . PLoS One, 2009, 4（3）：e4687.
[10] Swigut T, Wysocka J. H3K27 demethylases, at long last[J] . Cell, 2007, 131（1）：29-32.
[11] Zhang F, Xu L, Xu L, et al. Histone demethylase JMJD3 is required for osteoblast differentiation in mice[J] . Sci Rep, 2015, 5：13418.
[12] Iida A, Iwagawa T, Kuribayashi H, et al. Histone demethylase Jmjd3is required for the development of subsets of retinal bipolar cells[J] . Proc Natl Acad Sci USA, 2014, 111：3751-3756.
[13] Zhao W, Li Q, Ayers S, et al. Jmjd3 inhibits reprogramming by up regulating expression of INK4a/Arf and targeting PHF20 for ubiquitination[J] . Cell, 2013, 152（5）：1073-1050.
[14] Tanaka Y, Yano H, Ogasawara S, et al. Mild glucose starvation induces KDM2A-mediated H3K36me2 demethylation through AMPK to reduce rRNA transcription and cell proliferation[J] . Mol Cell Biol, 2015, 35（24）：4170-4184.
[15] Janzer A, Stamm K, Becker A, et al. The H3K4me3 histone demethylase fbxl10 is a regulator of chemokine expression, cellular morphology, and the metabolome of fibroblasts[J] . Journal of Biological Chemistry, 2012, 287（37）：30984-3092.
[16] Herzog M, Josseaux E, et al. The histone demethylase Kdm3a is essential to progression through differentiation[J] . Nucleic Acids Res, 2012, 40（15）：7219-7232.
[17] Ling Y, Fan Z, Bo Y, et al. Histone Demethylases KDM4B and KDM6B Promotes Osteogenic Differentiation of Human MSCs[J] . Cell Stem Cell, 2012, 11（1）：50.
[18] Su Z, Wang F, Lee JH, et al. Reader domain specificity and lysine demethylase-4 family function[J] . Nature Communications, 2016, 7：13387.
[19] Pack LR, Yamamoto KR, Fujimori DG. Opposing Chromatin Signals Direct and Regulate the Demethylase Activity of KDM4C[J] . J Biol Chem, 2016, 291（12）：6060-6070.
[20] Kupershmit I, Khouryhaddad H, Awwad S W, et al. KDM4C（GASC1）lysine demethylase is associated with mitotic chromatin and regulates chromosome segregation during mitosis. [J] . Nucleic Acids Research, 2014, 42（10）：6168-6182.
[21] Zoabi M, Nadar-Ponniah PT, Khoury-Haddad H, et al. RNA-dependent chromatin localization of KDM4D lysine demethylase promotes H3K9me3 demethylation[J] . Nucleic Acids Research, 2014, 42（21）：13026.
[22] Wang C, Wang J, et al. KDM5A controls bone morphogenic protein 2-induced osteogenic differentiation of bone mesenchymal stem cells during osteoporosis[J] . Cell Death Dis, 2016, 7（8）：e2335.
[23] Wang D, Han S, Peng R, et al. Depletion of histone demethylase KDM5B inhibits cell proliferation of hepatocellular carcinoma by regulation of cell cycle checkpoint proteins p15 and p27. [J] . J Exp Clini Cancer Res, 2016, 35（1）：1-13.
[24] Jiang W, Wang J, Zhang Y. Histone H3K27me3 demethylases KDM6A and KDM6B modulate definitive endoderm differentiation from human ESCs by regulating WNT signaling pathway[J] . Cell Research, 2013, 23（1）：122-130.
[25] Pan MR, Hsu MC, Chen LT, et al. G9a orchestrates PCL3 and KDM7A to promote histone H3K27 methylation[J] . Scientific Reports, 2015, 5：18709.
[26] Feng W, Yonezawa M, Ye J, et al. PHF8 activates transcription of rRNA genes through H3K4me3 binding and H3K9me1/2 demethylation[J] . Nat Struct Mol Biol, 2010, 17：445-450.
[27] Qi HH, Sarkissian M, Hu GQ, et al. Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development[J] . Nature, 2010, 466：503-507.
[28] Chen B, Yu M, et al. Mdig de-represses H19 large intergenic non-coding RNA（lincRNA）by down-regulating H3K9me3 and heterochromatin[J] . Oncotarget, 2013, 4（9）：1427.
[29] Lee KH, Ju UI, Song JY, et al. The histone demethylase PHF2 promotes fat cell differentiation as an epigenetic activator of both C/EBPα and C/EBPδ. [J] . Mol Cells, 2014, 37（10）：734.
[30] Chen Q, Sinha K, Deng JM, et al. Mesenchymal deletion of histone demethylase NO66 in mice promotes bone formation[J] . J Bone Miner Res, 2015, 30（9）：1608-1617.
[31] Burgold T, Spreafico F, De Santa F, et al. The histone H3 lysine 27-specific demethylase JMJD3 is required for neural commitment[J] . PLoS One, 2008, 3（8）：e3034.
[32] GaoY, Hyttel P, Hall VJ. Regulation of H3K27me3 and H3K4me3 during early porcine embryonic development[J] . Mol Reprod Dev, 2010, 77（6）：540- 549.
[33] Canovas S, Cibelli JB, Ross PJ. Jumonji domain-containing protein 3 regulates histone3 lysine 27 methylation during bovine preimplantation development[J] . Proc Natl Acad Sci USA, 2012, 109（7）：2400-2405.
[34] Kartikasari AE, Zhou JX, Kanji MS, et al. The histone demethylase Jmjd3 sequentially associates with the transcription factors Tbx3 and Eomes to drive endoderm differentiation[J] . Embo J, 2013, 32（10）：1393-1408.
[35] Dahle, Kumar A, Kuehn MR. Nodal signaling recruits the histone demethylase Jmjd3 to counteract polycomb-mediated repression at target genes[J] . Sci Signal, 2010, 3（127）：ra48.
[36] Satoh T, Takeuchi O, Vandenbon A, et al. The Jmjd3-Irf4 axisregulates M2 macrophage polarization and host responses against helminthinfection[J] . Nat Immun, 2010, 11：936-944.
[37] Morales Torres C, Laugesen A, Helin K. Utx is required for proper induction of ectoderm andmesoderm during differentiation of embryonic stem cells[J] . PLoS One, 2013；8：e60020.
[38] Ohtani K, Zhao C, Dobreva G, et al. Jmjd3 controls mesodermal andcardiovascular differentiation of embryonic stem cells[J] . Circ Res, 2013, 113：856-862.
[39] Zhang F, Xu L, Xu L, et al. JMJD3 promotes chondrocyte proliferation and hypertrophy during endochondral bone formation in mice[J] . J Mol Cell Biol, 2015, 7（1）：23-34.
[40] Gomez-Sanchez JA, Gomis-Coloma C, Morenilla-Palao C, et al. Epigenetic induction of the Ink4a/Arf locus prevents Schwann cell overproliferation during nerveregeneration and after tumorigenic challenge[J] . Brain：J Neurol, 2013；136：2262-2278.
[41] Huszar JM, Payne CJ. MIR146A inhibits JMJD3 expression and osteogenic differentiation in human mesenchymal stem cells[J] . FEBS Lett, 2014, 588（9）：1850-1856.
[42] Xu J, Yu B, Hong C, Wang CY. KDM6B epigenetically regulates odontogenic differentiation of dentalmesenchymal stem cells[J] . Int J Oral Sci, 2013, 5：200-205.
[43] 张妍. JMJD3调控弥漫性大B细胞淋巴瘤进展的作用机制研究[D] . 天津：南开大学, 2014.
[44] Liu Z, Cao W, Xu L, et al. The histone H3 lysine-27 demethylase Jmjd3 plays a critical role in specific regulation of Th17 cell differentiation[J] . J Mol Cell Biol, 2015, 7（6）：505-516.
[45] De Santa F, Totaro MG, et al. The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing[J] . Cell, 2007, 130（6）：1083-1094.
[46] Dai JP, Lu JY, Zhang Y, et al. Jmjd3 activates Mash1 gene in RA induced neuronal differentiation of P19 cell[J] . J Cell Biochem, 2010, 110：1457-1463.
[47] Akizu N, Estaras C, Guerrero L, et al. H3K27me3 regulates BMP activity indeveloping spinal cord[J] . Development（Cambridge, England）, 2010, 137：2915-2925.
[48] Fonseca MB, Nunes AF, Morgado AL, et al. TAp63γ demethylation regulates protein stability and cellular distribution during neural stem cell differentiation[J] . PLoS One, 2012, 7（12）：e52417.
[49] Sen GL, Webster DE, Barragan DI, et al. Control of differentiationin a self-renewing mammaliantissue by the histonedemethylase JMJD3[J] . Genes Dev, 2008, 22（14）：1865-1870.
[50] Jung JW, et al. Histone deacetylase controls adult stem cell aging by balancing the expression of polycomb genes and jumonji domain containing 3[J] . Cell Mol Life Sci, 2010, 67（7）：1165-1176.
[51] Agger K, Cloos PA, Rudkjaer L, et al. The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence[J] . Genes & Development, 2009, 23（10）：1171-1176.
[52] Barradas M, Anderton E, Acosta JC, et al. Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS[J] . Genes Dev, 2009, 23（10）：1177-1182.
[53] Agherbi H, Gaussmann-Wenger A, et al. Polycomb mediated epigenetic silencing and replication timing at the INK4a/ARF locus during senescence[J] . PLoS One, 2009, 4（5）：e5622.
[54] Chandra T, Kirschner K, Thuret JY, et al. Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation[J] . Mol Cell, 2012, 47（2）：203-214.
[55] Di Micco R, Sulli G, Dobreva M, et al. Interplay between oncogene-induced DNA damage response and heterochromatin in senescence and cancer[J] . Nat Cell Boil, 2011, 13（3）：292-302.
[56] Wang Z, Liu Y, Takahashi M, et al. N terminus of ASPP2 binds to Ras and enhances Ras/Raf/MEK/ERK activation to promote oncogene-induced senescence[J] . Proc Natl Acad Sci USA, 2013, 110（1）：312-317.
[57] Campisi J, d’AddadiFagagna F. Cellular senescence：when bad things happen to good cells[J] . Nat Rev Mol Cell Biol, 2007, 8（9）：729-740.
[58] Kim WY, Sharpless NE. The regulation of INK4/ARF in cancer and aging[J] . Cell, 2006, 127（2）：265-275.
[59] Yang Q, Tian Y, Ostler KR, et al. Epigenetic alterations differ in phenotypically distinct human neuroblastoma cell lines[J] . BMC Cancer, 2010, 10：286.
[60] He LR, Liu MZ, et al. Prognostic impact of H3K27me3 expression-onlocoregional progression after chemoradiotherapy in esophageal squamous cellcarcinoma[J] . BMC Cancer, 2009, 9：461.
[61] Lu TY, Kao CF, Lin CT, et al. DNA methylation and histone modif-icationregulate silencing of OPG during tumor progression[J] . J Cell Biochem, 2009, 108（1）：315-325.
[62] 杨琳. 真核表达载体过表达 JMJD3 基因对急性白血病HL-60 细胞株影响的实验研究[D] . 福州：福建医科大学, 2014.
[63] Shen Y, Guo X, Wang Y, et al. Expression and significance of histone H3K27 demethylases in renal cell carcinoma[J] . BMC Cancer, 2012, 12：470.
[64] Anderton JA, Bose S, et al. The H3K27me3 demethylase, KDM6B, is induced by Epstein-Barr virus and over-expressed in Hodgkin’s Lymphoma[J] . Oncogene, 2011, 30（17）：2037-2043.
[65] Svotelis A, Bianco S, Madore J, et al. H3K27 demethylation by JMJD3 at a poised enhancer of anti-apoptotic gene BCL2 determines ER alpha ligand dependency[J] . Embo J, 2011, 30（19）：3947-3961.
[66] Sola S, Xavier JM, Santos DM, et al. p53 interaction with JMJD3 results in its nuclear distribution during mouse neural stem cell differentiation[J] . PLoS One, 2011, 6（3）：el8421.