细胞自噬发生的表观遗传调节

doi:10.3724/SP.J.1005.2014.0447

遗传 ›› 2014, Vol. 36 ›› Issue (5): 447-455.doi: 10.3724/SP.J.1005.2014.0447

细胞自噬发生的表观遗传调节

孙源超^1,2, 秦训思¹, 陈宏², 沈伟¹

1. 青岛农业大学动物科技学院, 山东省高校动物生殖与种质创新重点实验室, 青岛 266109;
2. 西北农林科技大学动物科技学院, 陕西省农业分子生物学重点实验室, 杨凌 712100

收稿日期:2013-10-22 修回日期:2014-01-16 出版日期:2014-05-20 发布日期:2014-05-25
通讯作者: 沈伟, 博士, 教授, 博士生导师, 研究方向：生殖细胞生物学。E-mail: shenwei427@163.com E-mail:shenwei427@163.com
作者简介:孙源超, 博士研究生, 研究方向：生殖细胞生物学。E-mail: sycdeyx1@163.com
基金资助:
教育部新世纪优秀人才支持计划(编号：NCET-12-1026)和山东省自然科学杰出青年基金项目(编号：JQ201109)资助

Epigenetic control of autophagy

Yuanchao Sun^1,2 , Xunsi Qin¹, Hong Chen², Wei Shen¹

1. Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, China;
2. Key Laboratory of Agricultural Molecular Biology of Shanxi, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China

Received:2013-10-22 Revised:2014-01-16 Online:2014-05-20 Published:2014-05-25

摘要/Abstract

摘要：

细胞自噬是一种进化上保守的, 通过吞噬降解自身大分子物质或细胞器来维持细胞生存的活动。自噬与多种生命活动息息相关, 其功能的紊乱往往会导致肿瘤发生、神经退行性疾病、微生物感染等疾病。研究表明, 表观遗传修饰可以调控细胞自噬的发生, 并在细胞自噬的生物学功能调节过程中发挥重要作用, 但具体调控机制尚需进一步探究。文章综述了细胞自噬发生过程中存在的表观遗传效应, 包括组蛋白乙酰化对细胞自噬激活或抑制的负反馈调控, 通过DNA甲基化调节自噬相关基因活性来影响细胞自噬的发生, miRNA通过靶向调节自噬相关基因表达来影响组蛋白修饰, 从而调控细胞自噬的发生及作用过程等, 旨在为人们进一步研究细胞自噬发生过程中的表观遗传修饰及其机制提供信息依据。

关键词: 自噬, 表观遗传, DNA甲基化, 组蛋白修饰, miRNA

Abstract:

Autophagy is an evolutionarily conserved cellular process through cell degradation of own protein aggregates or organelles to survive. Autophagy is closely related to many life activities, and especially, its dysfunctions might cause many diseases and physiological problems, such as tumorigenesis, neurodegeneration and microbial infection. In recent years, many studies found that epigenetic modifications may regulate the occurrence of autophagy and also play an important role in the process of autophgy biological function.However the exact mechanism of epigenetic modifications remains largely unknown. Here,we review the epigenetic effects on regulation of autophagy process, including histone acetylation activation and negatively feedback controlling autophagy, DNA methylation regulating cell autophagy process by changing autophagy related genes, and miRNA regulating autophagy related gene expression by targeted degradation and histone modifications. This review will help understand the relationship between epigenetic effects and autophagy.

Key words: autophagy, epigenetic effects, DNA methylation, histone modification, miRNA

孙源超, 秦训思, 陈宏, 沈伟. 细胞自噬发生的表观遗传调节[J]. 遗传, 2014, 36(5): 447-455.

Yuanchao Sun, Xunsi Qin, Hong Chen, Wei Shen. Epigenetic control of autophagy[J]. HEREDITAS(Beijing), 2014, 36(5): 447-455.

参考文献

[1] Esclatine A, Chaumorcel M, Codogno P. Macroautophagy signaling and regulation. Curr Top Microbiol Immunol, 2009, 335: 33–70. <\p>

[2] Klionsky DJ. The molecular machinery of autophagy: un-answered questions. J Cell Sci, 2005, 118(Pt 1): 7–18. <\p>

[3] Walsh CM, Edinger AL. The complex interplay between autophagy, apoptosis, and necrotic signals promotes T-cell homeostasis. Immunol Rev, 2010, 236(1): 95–109. <\p>

[4] Tschan MP, Simon HU. The role of autophagy in antican-cer therapy: promises and uncertainties. J Intern Med, 2010, 268(5): 410–418. <\p>

[5] Zhuang W, Qin Z, Liang Z. The role of autophagy in sen-sitizing malignant glioma cells to radiation therapy. Acta Biochim Biophys Sin (Shanghai), 2009, 41(5): 341–351. <\p>

[6] Levine B, Yuan J. Autophagy in cell death: an innocent convict? J Clin Invest, 2005, 115(10): 2679–2688. <\p>

[7] Chen Y, Klionsky DJ. The regulation of autophagy-unanswered questions. J Cell Sci, 2011, 124(Pt 2): 161–170. <\p>

[8] Torres-Padilla ME, Parfitt DE, Kouzarides T, Zernicka- Goetz M. Histone arginine methylation regulates pluripotency in the early mouse embryo. Nature, 2007, 445(7124): 214– 218. <\p>

[9] Fraga MF, Ballestar E, Villar-Garea A, Boix-Chornet M, Espada J, Schotta G, Bonaldi T, Haydon C, Ropero S, Petrie K, Iyer NG, Pérez-Rosado A, Calvo E, Lopez JA, Cano A, Calasanz MJ, Colomer D, Piris MA, Ahn N, Im-hof A, Caldas C, Jenuwein T, Esteller M. Loss of acetyla-tion at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet, 2005, 37(4): 391–400. <\p>

[10] Füllgrabe J, Lynch-Day MA, Heldring N, Li WB, Struijk RB, Ma Q, Hermanson O, Rosenfeld MG, Klionsky DJ, Joseph B. The histone H4 lysine 16 acetyltransferase hMOF regulates the outcome of autophagy. Nature, 2013, 500(7463): 468–471. <\p>

[11] Carrozza MJ, Utley RT, Workman JL, Côté J. The diverse functions of histone acetyltransferase complexes. Trends Genet, 2003, 19(6): 321–329. <\p>

[12] Yan Y, Barlev NA, Haley RH, Berger SL, Marmorstein R. Crystal structure of yeast Esa1 suggests a unified mecha-nism for catalysis and substrate binding by histone acetyltransferases. Mol Cell, 2000, 6(5): 1195–1205. <\p>

[13] Yan Y, Harper S, Speicher DW, Marmorstein R. The cata-lytic mechanism of the ESA1 histone acetyltransferase involves a self-acetylated intermediate. Nat Struct Biol, 2002, 9(11): 862–869. <\p>

[14] Roth SY, Denu JM, Allis CD. Histone acetyltransferases. Annu Rev Biochem, 2001, 70: 81–120. <\p>

[15] Utley RT, Côté J. The MYST family of histone acetyltransferases. Curr Top Microbiol Immunol, 2003, 274: 203–236. <\p>

[16] Akhtar A, Becker PB. The histone H4 acetyltransferase MOF uses a C2HC zinc finger for substrate recognition. EMBO Rep, 2001, 2(2): 113–118. <\p>

[17] Bone JR, Lavender J, Richman R, Palmer MJ, Turner BM, Kuroda MI. Acetylated histone H4 on the male X chromo-some is associated with dosage compensation in Droso-phila. Genes Dev, 1994, 8(1): 96–104. <\p>

[18] Smith ER, Pannuti A, Gu WG, Steurnagel A, Cook RG, Allis CD, Lucchesi JC. The drosophila MSL complex ac-etylates histone H4 at lysine 16, a chromatin modification linked to dosage compensation. Mol Cell Biol, 2000, 20(1): 312–318. <\p>

[19] Akhtar A, Zink D, Becker PB. Chromodomains are pro-tein-RNA interaction modules. Nature, 2000, 407(6802): 405–409. <\p>

[20] Buscaino A, Köcher T, Kind JH, Holz H, Taipale M, Wagner K, Wilm M, Akhtar A. MOF-regulated acetylation of MSL-3 in the Drosophila dosage compensation com-plex. Mol Cell, 2003, 11(5): 1265–1277. <\p>

[21] Morales V, Straub T, Neumann MF, Mengus G, Akhtar A, Becker PB. Functional integration of the histone acetyltransferase MOF into the dosage compensation complex. EMBO J, 2004, 23(11): 2258–2268. <\p>

[22] Neal KC, Pannuti A, Smith ER, Lucchesi JC. A new hu-man member of the MYST family of histone acetyl trans-ferases with high sequence similarity to Drosophila MOF. Biochim Biophys Acta, 2000, 1490(1–2): 170–174. <\p>

[23] de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB. Histone deacetylases (HDACs): charac-terization of the classical HDAC family. Biochem J, 2003, 370(Pt 3): 737–749. <\p>

[24] Yang XJ, Seto E. Lysine acetylation: codified crosstalk with other posttranslational modifications. Mol Cell, 2008, 31(4): 449–461. <\p>

[25] Yang XJ, Seto E. The Rpd3/Hda1 family of lysine deace-tylases: from bacteria and yeast to mice and men. Nat Rev Mol Cell Biol, 2008, 9(3): 206–218. <\p>

[26] Martin M, Kettmann R, Dequiedt F. Class IIa histone deacetylases: regulating the regulators. Oncogene, 2007, 26(37): 5450–5467. <\p>

[27] Gregoretti IV, Lee YM, Goodson HV. Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J Mol Biol, 2004, 338(1): 17–31. <\p>

[28] Kaeberlein M, McVey M, Guarente L. The SIR2/3/4 com-plex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Gene Dev, 1999, 13(19): 2570–2580. <\p>

[29] Blander G, Guarente L. The Sir2 family of protein deace-tylases. Annu Rev Biochem, 2004, 73: 417–435. <\p>

[30] Vaquero A, Sternglanz R, Reinberg D. NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs. Onco-gene, 2007, 26(37): 5505–5520. <\p>

[31] Hajji N, Wallenborg K, Vlachos P, Füllgrabe J, Hermanson O, Joseph B. Opposing effects of hMOF and SIRT1 on H4K16 acetylation and the sensitivity to the topoisomerase II inhibitor etoposide. Oncogene, 2010, 29(15): 2192–2204. <\p>

[32] Vaquero A, Scher M, Lee D, Erdjument-Bromage H, Tempst P, Reinberg D. Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin. Mol Cell, 2004, 16(1): 93–105. <\p>

[33] Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, Guarente L, Weinberg RA. hSIR2SIRT1 func-tions as an NAD-dependent p53 deacetylase. Cell, 2001, 107(2): 149–159. <\p>

[34] Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science, 2004, 303(5666): 2011–2015. <\p>

[35] Zhao Y, Yang J, Liao W, Liu X, Zhang H, Wang S, Wang D, Feng J, Yu L, Zhu WG. Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nat Cell Biol, 2010, 12(7): 665–675. <\p>

[36] Yi C, Ma MS, Ran LL, Zheng JX, Tong JJ, Zhu J, Ma CY, Sun YF, Zhang SJ, Feng WZ, Zhu LY, Le Y, Gong XQ, Yan XQ, Hong B, Jiang FJ, Xie ZP, Miao D, Deng HT, Yu L. Function and molecular mechanism of acetylation in autophagy regulation. Science, 2012, 336(6080): 474–477. <\p>

[37] Bunney TD, Katan M. Phosphoinositide signalling in cancer: beyond PI3K and PTEN. Nat Rev Cancer, 2010, 10(5): 342–352. <\p>

[38] Corradetti MN, Inoki K, Bardeesy N, DePinho RA, Guan KL. Regulation of the TSC pathway by LKB1: evidence of a mo-lecular link between tuberous sclerosis complex and Peutz- Jeghers syndrome. Genes Dev, 2004, 18(13): 1533–1538. <\p>

[39] Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE, Shaw RJ. AMPK phos-phorylation of raptor mediates a metabolic checkpoint. Mol Cell, 2008, 30(2): 214–226. <\p>

[40] Degtyarev M, De Mazière A, Orr C, Lin J, Lee BB, Tien JY, Prior WW, van Dijk S, Wu H, Gray DC, Davis DP, Stern HM, Murray LJ, Hoeflich KP, Klumperman J, Friedman LS, Lin K. Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents. J Cell Biol, 2008, 183(1): 101–116. <\p>

[41] Arico S, Petiot A, Bauvy C, Dubbelhuis PF, Meijer AJ, Codogno P, Ogier-Denis E. The tumor suppressor PTEN positively regulates macroautophagy by inhibiting the phosphatidylinositol 3-kinase/protein kinase B pathway. J Biol Chem, 2001, 276(38): 35243–35246. <\p>

[42] Pattingre S, Tassa A, Qu XP, Garuti R, Liang XH, Mizu-shima N, Packer M, Schneider MD, Levine B. Bcl-2 an-tiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell, 2005, 122(6): 927–939. <\p>

[43] Kihara A, Kabeya Y, Ohsumi Y, Yoshimori T. Beclin- phosphatidylinositol 3-kinase complex functions at the trans-Golgi network. EMBO Rep, 2001, 2(4): 330–335. <\p>

[44] Zhong Y, Wang QJ, Li XT, Yan Y, Backer JM, Chait BT, Heintz N, Yue ZY. Distinct regulation of autophagic activ-ity by Atg14L and Rubicon associated with beclin 1-phosphatidylinositol-3-kinase complex. Nat Cell Biol, 2009, 11(4): 468–476. <\p>

[45] Li ZD, Chen B, Wu YQ, Jin F, Xia YJ, Liu XJ. Genetic and epigenetic silencing of the beclin 1 gene in sporadic breast tumors. BMC Cancer, 2010, 10: 98. <\p>

[46] Ahn CH, Jeong EG, Lee JW, Kim MS, Kim SH, Kim SS, Yoo NJ, Lee SH. Expression of beclin-1, an autophagy- related protein, in gastric and colorectal cancers. APMIS, 2007, 115(12): 1344–1349. <\p>

[47] Schnekenburger M, Grandjenette C, Ghelfi J, Karius T, Foliguet B, Dicato M, Diederich M. Sustained exposure to the DNA demethylating agent, 2'-deoxy-5-azacytidine, leads to apoptotic cell death in chronic myeloid leukemia by promoting differentiation, senescence, and autophagy. Biochem Pharmacol, 2011, 81(3): 364–378. <\p>

[48] Mizushima N. The role of the Atg1/ULK1 complex in autophagy regulation. Curr Opin Cell Biol, 2010, 22(2): 132–139. <\p>

[49] Chan EYW, Longatti A, McKnight NC, Tooze SA. Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism. Mol Cell Biol, 2009, 29(1): 157–171. <\p>

[50] Kabeya Y, Kamada Y, Baba M, Takikawa H, Sasaki M, Ohsumi Y. Atg17 functions in cooperation with Atg1 and Atg13 in yeast autophagy. Mol Biol Cell, 2005, 16(5): 2544–2553. <\p>

[51] Kamada Y, Yoshino K, Kondo C, Kawamata T, Oshiro N, Yonezawa K, Ohsumi Y. Tor directly controls the Atg1 kinase complex to regulate autophagy. Mol Cell Biol, 2010, 30(4): 1049–1058. <\p>

[52] Hosokawa N, Sasaki T, Iemura S, Natsume T, Hara T, Mizushima N. Atg101, a novel mammalian autophagy protein interacting with Atg13. Autophagy, 2009, 5(7): 973–979. <\p>

[53] Ganley IG, Lam du H, Wang J, Ding X, Chen S, Jiang X. ULK1. ATG13. FIP200 complex mediates mTOR signal-ing and is essential for autophagy. J Biol Chem, 2009, 284(18): 12297–12305. <\p>

[54] Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol, 2011, 13(2): 132–141. <\p>

[55] Li WJ, Li XL, Wang W, Li XY, Tan YX, Yi M, Yang JB, McCarthy JB, Xiong W, Wu MH, Ma J, Su B, Zhang ZP, Liao QJ, Xiang B, Li GY. NOR1 is an HSF1- and NRF1-regulated putative tumor suppressor inactivated by promoter hypermethylation in nasopharyngeal carcinoma. Carcinogenesis, 2011, 32(9): 1305–1314. <\p>

[56] Li WJ, Li XL, Wang W, Yi M, Zhou YH, Zheng P, Xiong W, Yang JB, Peng SP, McCarthy JB, Xiang B, Li GY. Tu-mor suppressor gene Oxidored-nitro domain-containing protein 1 regulates nasopharyngeal cancer cell autophagy, metabolism, and apoptosis in vitro. Int J Biochem Cell Biol, 2013, 45(9): 2016–2026. <\p>

[57] Hu XT, Sui XB, Li LL, Huang XF, Rong R, Su XW, Shi QL, Mo LJ, Shu XS, Kuang YY, Tao Q, He C. Protocadherin 17 acts as a tumour suppressor inducing tumour cell apoptosis and autophagy, and is frequently methylated in gastric and colorectal cancers. J Pathol, 2013, 229(1): 62–73. <\p>

[58] Bai H, Inoue J, Kawano T, Inazawa J. A transcriptional variant of the LC3A gene is involved in autophagy and frequently inactivated in human cancers. Oncogene, 2012, 31(40): 4397–4408. <\p>

[59] Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell, 2009, 136(2): 215–233. <\p>

[60] Mellios N, Huang HS, Grigorenko A, Rogaev E, Akbarian S. A set of differentially expressed miRNAs, including miR-30a-5p, act as post-transcriptional inhibitors of BDNF in prefrontal cortex. Hum Mol Genet, 2008, 17(19): 3030– 3042. <\p>

[61] Zhu H, Wu H, Liu X, Li B, Chen Y, Ren X, Liu CG, Yang JM. Regulation of autophagy by a beclin 1-targeted mi-croRNA, miR-30a, in cancer cells. Autophagy, 2009, 5(6): 816–823. <\p>

[62] Varambally S, Cao Q, Mani RS, Shankar S, Wang XS, Ateeq B, Laxman B, Cao XH, Jing XJ, Ramnarayanan K, Brenner JC, Yu JD, Kim JH, Han B, Tan P, Kumar-Sinha C, Lonigro RJ, Palanisamy N, Maher CA, Chinnaiyan AM. Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science, 2008, 322(5908): 1695–1699. <\p>

[63] Frankel LB, Wen JY, Lees M, Høyer-Hansen M, Farkas T, Krogh A, Jäättelä M, Lund AH. microRNA-101 is a potent inhibitor of autophagy. EMBO J, 2011, 30(22): 4628– 4641. <\p>

[64] Ravikumar B, Imarisio S, Sarkar S, O'Kane CJ, Rubinsztein DC. Rab5 modulates aggregation and toxicity of mutant huntingtin through macroautophagy in cell and fly models of Huntington disease. J Cell Sci, 2008, 121(Pt 10): 1649–1660. <\p>

[65] Mariño G, Uría JA, Puente XS, Quesada V, Bordallo J, López-Otín C. Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy. J Biol Chem, 2003, 278(6): 3671–3678. <\p>

[66] Guo LM, Pu Y, Han Z, Liu T, Li YX, Liu M, Li X, Tang H. MicroRNA-9 inhibits ovarian cancer cell growth through regulation of NF-κB1. FEBS J, 2009, 276(19): 5537–5546. <\p>

[67] Adams BD, Furneaux H, White BA. The micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen recep-tor-α (ERα) and represses ERα messenger RNA and pro-tein expression in breast cancer cell lines. Mol Endocrinol, 2007, 21(5): 1132–1147. <\p>

[68] ccaro AM, Sacco A, Jia XY, Azab AK, Maiso P, Ngo HT, Azab F, Runnels J, Quang P, Ghobrial IM. microRNA- dependent modulation of histone acetylation in Waldenstrom macroglobulinemia. Blood, 2010, 116(9): 1506–1514.<\p>

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细胞自噬发生的表观遗传调节

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