国际口腔医学杂志 ›› 2016, Vol. 43 ›› Issue (3): 318-324.doi: 10.7518/gjkq.2016.03.015

• 综述 • 上一篇    下一篇

表观遗传在牙发生和牙再生中的作用及意义

周晨1,凌均棨2   

  1. 1.中山大学光华口腔医学院?附属口腔医院正畸科 广东省口腔医学重点实验室 广州 510055;2.中山大学光华口腔医学院?附属口腔医院牙体牙髓病科 广东省口腔医学重点实验室 广州 510055
  • 收稿日期:2015-06-30 修回日期:2016-02-23 出版日期:2016-05-01 发布日期:2016-05-01
  • 通讯作者: 凌均棨,教授,博士,Email:lingjq@mail.sysu.edu.cn
  • 作者简介:周晨,博士,Email:zhouchen@mail2.sysu.edu.cn
  • 基金资助:
    国家自然科学基金(81170932);广东省领军人才专项经费(52000-3210002)

Epigenetics in tooth development and its implication in tooth regeneration

Zhou Chen1, Ling Junqi2   

  1. 1. Dept. of Orthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China; 2. Dept. of Conservative Dentistry and Endodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China) This study was supported by the National Natural Science Foundation of China(81170932)and Special Talents Fund in Guangdong Province(52000-3210002).
  • Received:2015-06-30 Revised:2016-02-23 Online:2016-05-01 Published:2016-05-01

摘要: 表观遗传是指DNA序列不发生变化,基因表达却发生了可遗传改变的一种遗传方式,主要涉及DNA甲基化和组蛋白的不同翻译后修饰,决定了特定的基因表达形式。DNA甲基化常引起基因表达抑制,而脱甲基化则引起基因表达开放。组蛋白有众多的共价修饰形式,根据修饰的种类、位点及个数的不同,引起基因沉默或激活。表观遗传修饰是细胞定向分化和重编程中基因特异性表达的重要调控方式,在机体发生中扮演着重要的角色。在牙发生过程中,表观遗传与传统的基因表达调控协同,调节细胞增殖、分化和迁移相关基因的时空表达,最后导致牙的形成。诠释牙发生过程中的表观遗传调控机制,无疑可为牙再生提供关键的线索和思路。

关键词: 牙发育, 基因表达调控, 表观遗传, 牙再生, 牙发育, 基因表达调控, 表观遗传, 牙再生

Abstract: Epigenetics, mainly including DNA methylation and histone post-translational modification, is the heritable changes that are not caused by changes in the DNA sequence; this change also alters how genes are expressed. DNA methylation typically causes gene transcriptional silencing, whereas demethylation leads to transcription activation. A large number of covalent modifications on histone, such as different types, residues, and amount, will affect the inhibition or activation of gene expression. Epigenetic modifications play pivotal roles in organogenesis by controlling gene expression during cell fate determination and reprogramming. In the process of tooth development, complex orchestration between genetic and epigenetic programs regulates the spatiotemporal expression of cell proliferation-, differentiation-, and migration-related genes, and finally tooth formation. Exploring the molecular biology of epigenetic, together with the epigenetic findings in tooth development, is not only fundamental but also inspiring for tooth regeneration.

Key words: tooth development, gene expression and regulation, epigenetics, tooth regeneration, tooth development, gene expression and regulation, epigenetics, tooth regeneration

中图分类号: 

  • Q 786
[1] Tucker A, Sharpe P. The cutting-edge of mammalian development; how the embryo makes teeth[J]. Nat Rev Genet, 2004, 5(7):499-508.
[2] Li Z, Yu M, Tian W. An inductive signalling network regulates mammalian tooth morphogenesis with implications for tooth regeneration[J]. Cell Prolif, 2013, 46(5):501-508.
[3] Jussila M, Thesleff I. Signaling networks regulating tooth organogenesis and regeneration, and the specification of dental mesenchymal and epithelial cell lineages[J]. Cold Spring Harb Perspect Biol, 2012, 4(4):a008425.
[4] Zhang YD, Chen Z, Song YQ, et al. Making a tooth: growth factors, transcription factors, and stem cells [J]. Cell Res, 2005, 15(5):301-316.
[5] Mitsiadis TA, Luder HU. Genetic basis for tooth malformations: from mice to men and back again[J]. Clin Genet, 2011, 80(4):319-329.
[6] Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals[J]. Nat Genet, 2003, 33 (Suppl):245-254.
[7] Orphanides G, Reinberg D. A unified theory of gene expression[J]. Cell, 2002, 108(4):439-451.
[8] Rakyan V, Whitelaw E. Transgenerational epigenetic inheritance[J]. Curr Biol, 2003, 13(1):R6.
[9] Hui T, Wang C, Chen D, et al. Epigenetic regulation in dental pulp inflammation[J]. Oral Dis, 2016, doi:10.1111/odi.12464.
[10] 李佳佳, 陈德桂. DNA甲基化修饰研究概述[J]. 中国细胞生物学学报, 2010, 32(2):189-192.
Li JJ, Chen DG. A summarization of DNA methyaltion modification research [J]. Chin J Cell Biol, 2010, 32(2):189-192.
[11] Santi DV, Garrett CE, Barr PJ. On the mechanism of inhibition of DNA-cytosine methyltransferases by cytosine analogs[J]. Cell, 1983, 33(1):9-10.
[12] Schubeler D. Function and information content of DNA methylation[J]. Nature, 2015, 517(7534):321-326.
[13] Bird AP. CpG-rich islands and the function of DNA methylation[J]. Nature, 1986, 321(6067):209-213.
[14] Smith ZD, Meissner A. DNA methylation: roles in mammalian development[J]. Nat Rev Genet, 2013, 14(3):204-220.
[15] Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond[J]. Nat Rev Genet, 2012, 13(7):484-492.
[16] Barreto G, Sch?fer A, Marhold J, et al. Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation[J]. Nature, 2007, 445(7128):671-675.
[17] Rai K, Huggins IJ, James SR, et al. DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45[J]. Cell, 2008, 135(7):1201-1212.
[18] Jin SG, Guo C, Pfeifer GP. GADD45A does not promote DNA demethylation[J]. PLoS Genet, 2008, 4(3):e1000013.
[19] Szwagierczak A, Bultmann S, Schmidt CS, et al. Sensitive enzymatic quantification of 5-hydroxymethylcytosine in genomic DNA[J]. Nucleic Acids Res, 2010, 38(19):e181.
[20] Williams K, Christensen J, Pedersen MT, et al. TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity[J]. Nature, 2011, 473(7347):343-348.
[21] Pastor WA, Pape UJ, Huang Y, et al. Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells[J]. Nature, 2011, 473(7347):394-397.
[22] Ficz G, Branco MR, Seisenberger S, et al. Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation[J]. Nature, 2011, 473(7347):398-402.
[23] Sun Z, Terragni J, Jolyon T, et al. High-resolution enzymatic mapping of genomic 5-hydroxymehytlcytosine in mouse embryonic stem cells[J]. Cell Rep, 2013, 3(2):567-576.
[24] Guo JU, Su Y, Zhong C, et al. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain[J]. Cell, 2011, 145(3):423-434.
[25] Kouzarides T. Chromatin modifications and their function[J]. Cell, 2007, 128(4):693-705.
[26] Chen T, Dent SY. Chromatin modifiers and remodellers: regulators of cellular differentiation[J]. Nat Rev Genet, 2014, 15(2):93-106.
[27] Peserico A, Simone C. Physical and functional HAT/ HDAC interplay regulates protein acetylation balance[J]. J Biom Biotechnol, 2011:1-10.
[28] Greer EL, Shi Y. Histone methylation: a dynamic mark in health, disease and inheritance[J]. Nat Rev Genet, 2012, 13(5):343-357.
[29] Rea S, Eisenhaber F, O’Carroll D, et al. Regulation of chromatin structure by site-specific histone H3 methyltransferases[J]. Nature, 2000, 406(6796):593-599.
[30] Jenuwein T, Allis CD. Translating the histone code [J]. Science, 2001, 293(5532):1074-1080.
[31] Rothbart SB, Strahl BD. Interpreting the language of histone and DNA modifications[J]. Biochim Biophys Acta, 2014, 1839(8):627-643.
[32] Yang Y, Bedford MT. Protein arginine methyltransferases and cancer[J]. Nat Rev Cancer, 2013, 13(1):37-50.
[33] 杜婷婷, 黄秋花. 组蛋白赖氨酸甲基化在表观遗传调控中的作用[J]. 遗传, 2007, 29(4):387-392.
Du TT, Huang QH. The roles of histone lysine methylation in epigenetic regulation[J]. Hereditas, 2007, 29(4):387-392.
[34] Townsend G, Rogers J, Richards L, et al. Agenesis of permanent maxillary lateral incisors in South Australian twins[J]. Aust Dent J, 1995, 40(3):186-192.
[35] Townsend G, Richards L, Hughes T. Molar intercuspal dimensions: genetic input to phenotypic variation[J]. J Dent Res, 2003, 82(5):350-355.
[36] Iglesias-Bartolome R, Callejas-Valera JL, Gutkind JS. Control of the epithelial stem cell epigenome: the shaping of epithelial stem cell identity[J]. Curr Opin Cell Biol, 2013, 25(2):162-169.
[37] Fan Z, Yamaza T, Lee JS, et al. BCOR regulates mesenchymal stem cell function by epigenetic mechanisms[J]. Nat Cell Biol, 2009, 11(8):1002-1009.
[38] Kamiunten T, Ideno H, Shimada A, et al. Coordinated expression of H3K9 histone methyltransferases during tooth development in mice[J]. Histochem Cell Biol, 2015, 143(3):259-266.
[39] Xu J, Yu B, Hong C, et al. KDM6B epigenetically regulates odontogenic differentiation of dental mesenchymal stem cells[J]. Int J Oral Sci, 2013, 5(4):200-205.
[40] Casagrande L, Demarco FF, Zhang Z, et al. Dentinderived BMP-2 and odontoblast differentiation[J]. J Dent Res, 2010, 89(6):603-608.
[41] Dong R, Yao R, Du J, et al. Depletion of histone demethylase KDM2A enhanced the adipogenic and chondrogenic differentiation potentials of stem cells from apical papilla[J]. Exp Cell Res, 2013, 319(18):2874-2882.
[42] Du J, Ma Y, Ma P, et al. Demethylation of epiregulin gene by histone demethylase FBXL11 and BCL6 corepressor inhibits osteo/dentinogenic differentiation[J]. Stem Cells, 2013, 31(1):126-136.
[43] Wang T, Liu H, Ning Y, et al. The histone acetyltransferase p300 regulates the expression of pluripotency factors and odontogenic differentiation of human dental pulp cells[J]. PLoS One, 2014, 9(7): e102117.
[44] Jin H, Park JY, Choi H, et al. HDAC inhibitor trichostatin A promotes proliferation and odontoblast differentiation of human dental pulp stem cells[J]. Tissue Eng Part A, 2013, 19(5/6):613-624.
[45] Mina M, Kollar EJ. The induction of odontogenesis in non-dental mesenchyme combined with early murine mandibular arch epithelium[J]. Arch Oral Biol, 1987, 32(2):123-127.
[46] Nakao K, Morita R, Saji Y, et al. The development of a bioengineered organ germ method[J]. Nat Methods, 2007, 4(3):227-230.
[47] Hu B, Nadiri A, Kuchler-Bopp S, et al. Tissue engineering of tooth crown, root, and periodontium[J]. Tissue Eng, 2006, 12(8):2069-2075.
[48] Mao JJ, Prockop DJ. Stem cells in the face: tooth regeneration and beyond[J]. Cell stem cell, 2012, 11(3):291-301.
[49] Papp B, Plath K. Epigenetics of reprogramming to induced pluripotency[J]. Cell, 2013, 152(6):1324-1343.
[50] Kim K, Doi A, Wen B, et al. Epigenetic memory in induced pluripotent stem cells[J]. Nature, 2010, 467(7313):285-290.
[51] Bar-Nur O, Russ HA, Efrat S, et al. Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells[J]. Cell Stem Cell, 2011, 9(1):17-23.
[52] Bhutani N, Brady JJ, Damian M, et al. Reprogramming towards pluripotency requires AID-dependent DNA demethylation[J]. Nature, 2010, 463(7284):1042-1047.
[53] Balana B, Nicoletti C, Zahanich I, et al. 5-Azacytidine induces changes in electrophysiological properties of human mesenchymal stem cells[J]. Cell Res, 2006, 16(12):949-960.
(本文采编 王晴)
[1] 陈荟宇,白明茹,叶玲. 信号素3A与口腔常见病关系的研究进展[J]. 国际口腔医学杂志, 2022, 49(5): 593-599.
[2] 马晓芳,黄永清,石冰,马坚. 双生子模型在唇腭裂病因学研究中的应用[J]. 国际口腔医学杂志, 2021, 48(5): 512-519.
[3] 张鑫, 汪成林, 杨静, 叶玲. 牙髓干细胞的表观遗传调控[J]. 国际口腔医学杂志, 2018, 45(3): 261-266.
[4] 刘双, 李纾. 表观遗传学及其调控与牙周病[J]. 国际口腔医学杂志, 2017, 44(5): 523-527.
[5] 李锋 谢小燕. 右侧下颌第四磨牙1例[J]. 国际口腔医学杂志, 2016, 43(1): 36-.
[6] 涂敏松1 李逸松2 代晓明2. DNA甲基化与口腔鳞状细胞癌的相关性研究进展[J]. 国际口腔医学杂志, 2016, 43(1): 79-.
[7] 班华杰1 王代友2. 细胞外信号调节激酶信号转导通路在牙发生和再生中的作用[J]. 国际口腔医学杂志, 2015, 42(6): 694-698.
[8] 吕琳琳 李纾. Yes相关蛋白基因在牙发育中的作用[J]. 国际口腔医学杂志, 2013, 40(6): 760-763.
[9] 雷丹 姜苏综述 吴亚菲 赵蕾审校. 表观遗传修饰和牙周病的相关性[J]. 国际口腔医学杂志, 2012, 39(2): 257-259.
[10] 吴煜综述 周学东审校. 细胞间连接在牙发育中的作用[J]. 国际口腔医学杂志, 2011, 38(3): 319-322.
[11] 马亮综述 王胜朝,张亚庆审校. 表观遗传学在牙齿形态发生中的作用[J]. 国际口腔医学杂志, 2010, 37(4): 447-450.
[12] 郭俊综述 杨健审校. 人牙根尖乳头干细胞及其在组织工程中的研究进展[J]. 国际口腔医学杂志, 2010, 37(4): 464-466.
[13] 程敏, 程琳, 冯志远, 李广义. 骨形态发生蛋白-2 在牙发育各阶段中的表达[J]. 国际口腔医学杂志, 2009, 36(6): 639-642.
[14] 中山大学光华口腔医学院·附属口腔医院牙体牙髓病科广东广州510055王劲茗综述 凌均棨审校. 报告基因及其在牙发育和牙再生研究中的应用[J]. 国际口腔医学杂志, 2009, 36(1): 105-105~107.
[15] 徐秀敏综述 梅陵宣审校. axin-2 与牙发育的关系[J]. 国际口腔医学杂志, 2008, 35(6): 675-675~677.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 王昆润. 修补颌骨缺损的新型生物学相容材料[J]. 国际口腔医学杂志, 1999, 26(06): .
[2] 陆加梅. 不可复性关节盘移位患者术前张口度与关节镜术后疗效的相关性[J]. 国际口腔医学杂志, 1999, 26(06): .
[3] 王昆润. 咀嚼口香糖对牙周组织微循环的影响[J]. 国际口腔医学杂志, 1999, 26(06): .
[4] 宋红. 青少年牙周炎外周血分叶核粒细胞的趋化功能[J]. 国际口腔医学杂志, 1999, 26(06): .
[5] 高卫民,李幸红. 发达国家牙医学院口腔种植学教学现状[J]. 国际口腔医学杂志, 1999, 26(06): .
[6] 侯锐. 正畸患者釉白斑损害的纵向激光荧光研究[J]. 国际口腔医学杂志, 1999, 26(05): .
[7] 轩东英. 不同赋形剂对氢氧化钙抗菌效果的影响[J]. 国际口腔医学杂志, 1999, 26(05): .
[8] 房兵. 唇腭裂新生儿前颌骨矫正方法及对上颌骨生长发育的影响[J]. 国际口腔医学杂志, 1999, 26(05): .
[9] 杨美祥. 前牙厚度在预测上下颌牙量协调性中的作用[J]. 国际口腔医学杂志, 1999, 26(04): .
[10] 赵艳丽. 手术刀、电凝、CO_2和KTP激光对大鼠舌部创口的作用[J]. 国际口腔医学杂志, 1999, 26(04): .