Advances of Tissue-specific Enhancers in Regulating SOX9 Expression

doi:10.3969/j.issn.1005-4979.2020.06.011

《Journal of Oral and Maxillofacial Surgery》 ›› 2020, Vol. 30 ›› Issue (6): 405-408. doi: 10.3969/j.issn.1005-4979.2020.06.011

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Advances of Tissue-specific Enhancers in Regulating SOX9 Expression

CHEN Qiming¹(), DAI Jiewen¹(), BIAN Qian²()

¹ Department of Oral and Cranio-maxillofacial Surgery, Shanghai Ninth People′s Hospital, Shanghai JiaoTong University School of Medicine, School of Stomatology, National Oral Disease Clinical Research Center, Shanghai Key Laboratory of Stomatology, Shanghai Institute of Stomatology
² Shanghai Institute of Precision Medicine, Shanghai 200011, China

Received:2020-01-31 Revised:2020-06-07 Online:2020-12-28 Published:2024-03-20

组织特异性增强子调控SOX9基因表达的研究进展

陈启铭¹(), 代杰文¹(), 卞迁²()

¹ 上海交通大学医学院附属第九人民医院·口腔医学院，口腔颅颌面科，国家口腔疾病临床研究中心，上海市口腔医学重点实验室，上海市口腔医学研究所
² 上海精准医学研究院，上海 200011

通讯作者: 代杰文，副主任医师. E-mail: daijiewen@163.com；卞迁，研究员. E-mail: qianbian@shsmu.edu.cn
作者简介:
陈启铭（1995—），男，江苏徐州人，硕士研究生. E-mail: carlchancc@foxmail.com
基金资助:
国家自然科学基金面上项目(82071097); 上海交通大学医学院附属第九人民医院精才培育项目(JC201804)

Abstract

Abstract:

As a master transcription factor regulating cartilage, craniofacial and gonad development, the expression level of SOX9 is strictly regulated in different tissues. Previous studies have well revealed that structural variations of non-coding regions around SOX9 are associated with cartilaginous abnormalities, craniofacial malformations and sex reversal, indicating different areas upstream of SOX9 could harbor various tissue-specific enhancers. Cartilage-specific enhancers of SOX9 include E84, E195, E250 and RCSE, whereas the E3 enhancer and F2 enhancer may activate SOX9 expression in craniofacial development, and Enh13 as well as TES are gonad specific enhancers of SOX9. More candidate tissue-specific enhancers of SOX9 could be identified through chromosome conformation capture techniques, chromatin accessibility analysis and species conservation analysis. In addition, functional study of these enhancers could shed light on the mechanism of regulating SOX9 gene expression and disease development.

Key words: SOX9, enhancer, cartilage development, craniofacial development, sex determination

摘要：

SOX9（SRY-related high-mobility-group-box gene 9）作为在软骨、颅颌面及性腺发育中的重要基因，在不同组织中的表达受到精细的调控。既往研究揭示了SOX9非编码区域的染色体结构异常同软骨发育障碍、颅颌面畸形、性别反转等表型相关，且SOX9基因上游不同区段内包含组织特异性调控其表达的增强子元件，如E84、E195、E250、RCSE等与SOX9在软骨组织的表达相关。E3、F2等增强子负责调控SOX9在颅颌面组织中的表达，而Enh13、TES等则为SOX9的性腺特异性增强子。通过染色质构象捕获、染色质开放性分析、种属间保守性分析等方法，可发掘更多调控SOX9在不同组织中表达的增强子。结合功能研究，有望进一步深入阐明组织特异性增强子在调控SOX9基因表达和疾病发生中的作用机制。

关键词: SOX9, 增强子, 软骨发育, 颅颌面发育, 性别决定

CHEN Qiming, DAI Jiewen, BIAN Qian. Advances of Tissue-specific Enhancers in Regulating SOX9 Expression[J]. 《Journal of Oral and Maxillofacial Surgery》, 2020, 30(6): 405-408.

陈启铭, 代杰文, 卞迁. 组织特异性增强子调控SOX9基因表达的研究进展[J]. 《口腔颌面外科杂志》, 2020, 30(6): 405-408.

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URL: https://journal06.magtech.org.cn/Jweb_joms/EN/10.3969/j.issn.1005-4979.2020.06.011

https://journal06.magtech.org.cn/Jweb_joms/EN/Y2020/V30/I6/405

References 30

[1]	唐君仪, 周冠楠, 谢志芳. 转录因子SOX9调控软骨发育的研究进展[J]. 医学研究杂志, 2013, 42(9): 19-20, 164.
[2]	胡向荣, 杨文君, 吴翔燕, 等. SOX9和CDX2在结直肠癌中的表达[J]. 中国中西医结合外科杂志, 2011, 17(6): 564-567.
[3]	Matsushita M, Kitoh H, Kaneko H, et al. A novel SOX9 H169Q mutation in a family with overlapping phenotype of mild campomelic dysplasia and small Patella syndrome[J]. Am J Med Genet A, 2013, 161A(10): 2528-2534. doi: 10.1002/ajmg.a.36134 pmid: 24038782
[4]	Gordon CT, Tan TY, Benko S, et al. Long-range regulation at the SOX9 locus in development and disease[J]. J Med Genet, 2009, 46(10): 649-656. doi: 10.1136/jmg.2009.068361 pmid: 19473998
[5]	Lecointre C, Pichon O, Hamel A, et al. Familial acampomelic form of campomelic dysplasia caused by a 960 kb deletion upstream of SOX9[J]. Am J Med Genet A, 2009, 149A(6): 1183-1189. doi: 10.1002/ajmg.a.32830 pmid: 19449405
[6]	Leipoldt M, Erdel M, Bien-Willner GA, et al. Two novel translocation breakpoints upstream of SOX9 define Borders of the proximal and distal breakpoint cluster region in campomelic dysplasia[J]. Clin Genet, 2007, 71(1): 67-75. doi: 10.1111/j.1399-0004.2007.00736.x pmid: 17204049
[7]	Benko S, Gordon CT, Mallet D, et al. Disruption of a long distance regulatory region upstream of SOX9 in isolated disorders of sex development[J]. J Med Genet, 2011, 48(12): 825-830. doi: 10.1136/jmedgenet-2011-100255 pmid: 22051515
[8]	Benko S, Fantes JA, Amiel J, et al. Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence[J]. Nat Genet, 2009, 41(3): 359-364. doi: 10.1038/ng.329 pmid: 19234473
[9]	Gibcus JH, Dekker J. The hierarchy of the 3D genome[J]. Mol Cell, 2013, 49(5): 773-782. doi: 10.1016/j.molcel.2013.02.011 pmid: 23473598
[10]	Franke M, Ibrahim DM, Andrey G, et al. Formation of new chromatin domains determines pathogenicity of genomic duplications[J]. Nature, 2016, 538(7624): 265-269. doi: 10.1038/nature19800
[11]	Despang A, Schöpflin R, Franke M, et al. Functional dissection of the SOX9-Kcnj2 locus identifies nonessential and instructive roles of TAD architecture[J]. Nat Genet, 2019, 51(8): 1263-1271. doi: 10.1038/s41588-019-0466-z pmid: 31358994
[12]	Furlong EEM, Levine M. Developmental enhancers and chromosome topology[J]. Science, 2018, 361(6409): 1341-1345. doi: 10.1126/science.aau0320 pmid: 30262496
[13]	陈少坚, 郭风劲. SOX9基因促软骨形成作用机制研究进展[J]. 国际骨科学杂志, 2010, 31(2): 65-67.
[14]	Yao BJ, Wang QQ, Liu CF, et al. The SOX9 upstream region prone to chromosomal aberrations causing campomelic dysplasia contains multiple cartilage enhancers[J]. Nucleic Acids Res, 2015, 43(11): 5394-5408. doi: 10.1093/nar/gkv426 pmid: 25940622
[15]	Mochizuki Y, Chiba T, Kataoka K, et al. Combinatorial CRISPR/Cas9 approach to elucidate a far-upstream enhancer complex for tissue-specific Sox9 expression[J]. Dev Cell, 2018, 46(6): 794-806 doi: S1534-5807(18)30635-X pmid: 30146478
[16]	Santagati F, Rijli FM. Cranial neural crest and the building of the vertebrate head[J]. Nat Rev Neurosci, 2003, 4(10): 806-818. doi: 10.1038/nrn1221 pmid: 14523380
[17]	Mori-Akiyama Y, Akiyama H, Rowitch DH, et al. SOX9 is required for determination of the chondrogenic cell lineage in the cranial neural crest[J]. Proc Natl Acad Sci USA, 2003, 100(16): 9360-9365. doi: 10.1073/pnas.1631288100 pmid: 12878728
[18]	Benko S, Fantes JA, Amiel J, et al. Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence[J]. Nat Genet, 2009, 41(3): 359-364. doi: 10.1038/ng.329 pmid: 19234473
[19]	Satokata I, Maas R. Msx1 deficient mice exhibit cleft palate and abnormalities of craniofacial and tooth development[J]. Nat Genet, 1994, 6(4): 348-356. doi: 10.1038/ng0494-348 pmid: 7914451
[20]	Cai JL, Ash D, Kotch LE, et al. Gene expression in pharyngeal arch 1 during human embryonic development[J]. Hum Mol Genet, 2005, 14(7): 903-912. pmid: 15703188
[21]	Gordon CT, Attanasio C, Bhatia S, et al. Identification of novel craniofacial regulatory domains located far upstream of SOX9 and disrupted in Pierre Robin sequence[J]. Hum Mutat, 2014, 35(8): 1011-1020. doi: 10.1002/humu.22606 pmid: 24934569
[22]	Bagheri-Fam S, Barrionuevo F, Dohrmann U, et al. Long-range upstream and downstream enhancers control distinct subsets of the complex spatiotemporal SOX9 expression pattern[J]. Dev Biol, 2006, 291(2): 382-397. pmid: 16458883
[23]	Koopman P, Gubbay J, Vivian N, et al. Male development of chromosomally female mice transgenic for Sry[J]. Nature, 1991, 351(6322): 117-121. doi: 10.1038/351117a0
[24]	Vidal VP, Chaboissier MC, de Rooij DG, et al. SOX9 induces testis development in XX transgenic mice[J]. Nat Genet, 2001, 28(3): 216-217. doi: 10.1038/90046 pmid: 11431689
[25]	Sekido R, Lovell-Badge R. Sex determination involves synergistic action of SRY and SF1 on a specific SOX9 enhancer[J]. Nature, 2008, 453(7197): 930-934. doi: 10.1038/nature06944
[26]	Gonen N, Quinn A, O'Neill HC, et al. Normal levels of Sox9 expression in the developing mouse testis depend on the TES/TESCO enhancer, but this does not act alone[J]. PLoS Genet, 2017, 13(1)
[27]	Gonen N, Futtner CR, Wood S, et al. Sex reversal following deletion of a single distal enhancer of SOX9[J]. Science, 2018, 360(6396): 1469-1473. doi: 10.1126/science.aas9408 pmid: 29903884
[28]	Croft B, Ohnesorg T, Hewitt J, et al. Human sex reversal is caused by duplication or deletion of core enhancers upstream of SOX9[J]. Nat Commun, 2018, 9(1): 5319. doi: 10.1038/s41467-018-07784-9 pmid: 30552336
[29]	Bai XF, Shi SS, Ai B, et al. ENdb: a manually curated database of experimentally supported enhancers for human and mouse[J]. Nucleic Acids Res, 2020, 48(D1): 51-57. doi: 10.1093/nar/gkz973 pmid: 31665430
[30]	Frazer KA, Pachter L, Poliakov A, et al. VISTA: Computational tools for comparative genomics[J]. Nucleic Acids Res, 2004, 32(Web Server issue): w273-w279.

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