特异 AT 序列结合蛋白 2(SATB2) 的研究进展

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1 HEREDITAS (Beijing) , 33(9): ISSN 综述 DOI: /SP.J 特异 AT 序列结合蛋白 2(SATB2) 的研究进展 1, 钱琰琰 2, 王慧君 2, 马端 1., ; 2.,, , 2 特异 AT 序列结合蛋白 2(SATB2) 是与核基质结合区结合的转录因子, 在转录调控和染色质重组等过程中发挥重要作用 SATB2 是成骨细胞分化和骨基质形成过程中的关键调控分子, 其突变可导致先天性颌面部畸形的发生 ; SATB2 是中枢神经系统发育过程中的核心分子, 在胼胝体 脑桥等正常发育中起重要作用 ; SATB2 也参与肿瘤的发生, 在乳腺癌等恶性肿瘤中的表达升高 文章就上述各领域中 SATB2 的研究进展进行了综述 SATB2; 调控因子 ; 骨骼系统发育 ; 中枢神经系统发育 ; 肿瘤 Study progress of special AT-rich sequence binding protein 2 QIAN Yan-Yan 1, 2, WANG Hui-Jun 2, MA Duan 1,2 1. Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai , China; 2. Institutes of Biomedical Science, Resaerch Center for Birth Defects, Fudan University, Shanghai , China Abstract: SATB2 is a transcription factor, which plays an important role in transcriptional regulation and chromatin recombinant by combining with matrix attachment regions. SATB2 is a key regulatory molecule in the progress of osteoblast differentiation and bone matrix formation. Mutations in this gene are associated with congenital craniofacial malformation. In addition, SATB2 is involved in the development of central nervous system, especially the corpus callosum and the pons. At the same time, SATB2 may participate in the process of tumor formation. In malignant tumors, such as breast cancer, the expression level of SATB2 is higher than normal. The literatures of SATB2 were reviewed in this article. Keywords: SATB2; regulator; bone development; central nervous system development; tumor DNA (Scaffold/matrix attachment regions, MARs S/MARs) AT (Special AT-rich sequence binding protein)satb1 SATB2 MARs SATB1 DNA MARs 收稿日期 : ; 修回日期 : 基金项目 : ( 10JC ) 作者简介 :,, szhqianyanyan@163.com,, huijunwang@fudan.edu.cn 通讯作者 :,,, duanma@shmu.edu.cn 网络出版时间 : :48:07 URL:

2 948 HEREDITAS (Beijing) SATB2 2 33, 191 kb, 11, 733, 82 kda, SATB2 C SATB2 DNA -, DNA (MAR),,,, (Histone deacetylases, HDACs) (Histone acetyltransferases, HATs), SATB2, SATB2, SATB2 2q33.1 [1] Satb2 SATB2, SATB2 [2~4] Ahn [4], Satb2, Satb2 Dobreva [5] B (pre2 B cells) SATB2 µ MAR, µ SATB2 SUMO, SATB2, SUMO SATB2 Hassana [6] mir23a mir27a mir24-2 SATB2 3 UTR, SATB2 1 SATB2, SATB2 Satb2, SATB2 (Translocation),, SATB2, a2 (Homeoboxa2, Hoxa2) [7] (Phenytoin) Satb2, Hoxa2 [8] Satb2 : 4 (Activating transcription factor 4, Atf4) (Runt-related transription factor 2, Runx2),, (Bone sialoprotein, Bsp) (Osteocalcin, Ocn), [7, 9] Satb2 Runx2 Atf4 DNA, Satb2,, Runx2 (Osterix, Osx) Atf4 [6, 7, 9, 10], 1 图 1 成骨细胞分化过程中相关转录因子的调控作用,,, mir cluster mir23a mir27a mir Satb2, Pax9 Alx4 Msx1 3 [11],, 1/700~1/1000, 1.86 [12~14] TGFA MSX1 TGFB3 RARA BCL3 [13, 15], SATB2 [14] Satb2, Satb2 2q32-q33 [11], Fitzpatrick [12] SATB2 2q33.1 [1, 16], SATB2,

3 9 : AT 2(SATB2) 949, SATB2 [17] 1.2, SATB2 SATB2 [18, 19] 1.3 Toriello Carey Toriello Carey (TCS) (OMIM217980), ( ) TCS 2q33.1 (Breakpoint), SATB2 [20] SATB2 TCS 2.1 ( ), MARs [22] Satb2, [27], Satb2, Satb2, β-, Ctip2 [27] Satb2 Ctip2 [27~29], Satb2,, Fezf2-Ctip2 Satb2 [28~31] 2 2 SATB2,,, Satb2 [21] ;, Satb2 Lbx1 Isl1 [22] Satb2 MARs, Satb2 1(Histone deacetylase 1, HDAC1) 2(Metastasisassociated protein2, MTA2), [23] SATB2, FGF8 [24], Fgf8, [25] SATB2, (Ventromedial hypothalamus, VMH), [26] 图 2 神经元投射中转录因子间的相互作用, 2.2 (Parabrachial nuclei, PBN), PBN, PBN Satb2 PBN, [32],,, SATB2,, SATB2 Satb2 Ctip2, Foxp1 III-V Foxp1,, [31]

4 950 HEREDITAS (Beijing) SATB2 3.1 SATB1, SATB1,,, [33~35] SATB1, SATB2, SATB2, [33] SATB1 SATB2 4(IL-4) 13(IL-13) MAF1, 3 [35] 3.2, Xist RNA X Agrelo [36] Xist, Xist SATB1, SATB1 SATB2 X, SATB1 SATB2, Xist X 3.3, 90% (Head and neck squamous cell carcinomas, HNSCCs) ΔNp63α HNSCCs, TA p63 [37], SATB2 ΔNp63α, SATB2 HNSCCs SATB2 ΔNp63α p53 p63 p73, p53, SATB2 ΔNp63α HNSCC [38], SATB2,, 146 (Colorectal cancer, CRC), SATB2, SATB2 CRC [39] 4 SATB2, SATB2, SATB1, SATB2 参考文献 (References): [1] Rosenfeld JA, Ballif BC, Lucas A, Spence EJ, Powell C, Aylsworth AS, Torchia BA, Shaffer LG. Small deletions of SATB2 cause some of the clinical features of the 2q33.1 microdeletion syndrome. PLoS One, 2009, 4(8): e6568. [2] Brugmann SA, Powder KE, Young NM, Goodnough LH, Hahn SM, James AW, Helms JA, Lovett M. Comparative gene expression analysis of avian embryonic facial structures reveals new candidates for human craniofacial disorders. Hum Mol Genet, 2010, 19(5): [3] Depew MJ, Compagnucci C. Tweaking the hinge and caps: testing a model of the organization of jaw. J Exp Zool B Mol Dev Evol, 2008, 310B(4): [4] Ahn HJ, Park Y, Kim S, Park HC, Seo SK, Yeo SY, Geum D. The expression profile and function of Satb2 in zebrafish embryonic development. Mol Cells, 2010, 30(4): [5] Dobreva G, Dambacher J, Grosschedl R. SUMO modification of a novel MAR-binding protein, SATB2, modulates immunoglobulin μ gene expression. Genes Dev, 2003, 17(24): [6] Hassan MQ, Gordon JAR, Beloti MM, Croce CM, van Wijnen AJ, Stein JL, Stein GS, Lian JB. A network connecting Runx2, SATB2, and the mir-23a~27a~24-2 cluster regulates the osteoblast differentiation program. Proc Natl Acad Sci USA, 2010, 107(46): [7] Dobreva G, Chahrour M, Dautzenberg M, Chirivella L, Kanzler B, Fariñas I, Karsenty G, Grosschedl R. SATB2 is a multifunctional determinant of craniofacial patterning and osteoblast differentiation. Cell, 2006, 125(5): [8] Mao XY, Tang SJ. Effects of phenytoin on Satb2 and Hoxa2 gene expressions in mouse embryonic craniofacial tissue. Biochem Cell Biol, 2010, 88(4): [9] Ellies DL, Krumlauf R. Bone formation: The nuclear matrix reloaded. Cell, 2006, 125(5):

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