CTCF

轉錄阻抑物CTCF，也被稱為11鋅指蛋白或CCCTC結合因子，是由人類CTCF基因編碼的轉錄因子^[1][2]。CTCF參與多個細胞進程，包括轉錄調控、絕緣子活性調控、V(D)J重組、染色質結構調控等^[3][4]。

CCCTC-結合因子（鋅指蛋白）
PDB rendering based on 1x6h.
有效結構 PDB 直系同源檢索：PDBe, RCSB PDB查詢代碼列表 1X6H, 2CT1
標識
代號	CTCF
擴展標識	遺傳學：604167 鼠基因：109447 同源基因：4786 GeneCards: CTCF Gene
基因本體論描述 分子功能 · sequence-specific DNA binding transcription factor activity · transcription corepressor activity · protein binding · zinc ion binding · chromatin insulator sequence binding · sequence-specific DNA binding · transcription regulatory region DNA binding 細胞成分 · chromosome, centromeric region · condensed chromosome · nucleus · nucleoplasm · nucleolus 生物過程 · regulation of gene expression by genetic imprinting · transcription, DNA-dependent · chromosome segregation · maintenance of DNA methylation · positive regulation of gene expression · chromatin modification · nucleosome positioning · regulation of histone methylation · regulation of histone acetylation · regulation of gene expression, epigenetic · regulation of molecular function, epigenetic · negative regulation of transcription, DNA-dependent · positive regulation of transcription, DNA-dependent · regulation of centromeric sister chromatid cohesion Sources: Amigo / QuickGO
RNA表現模式
更多表現資料
直系同源體
物種	人類	小鼠
Entrez	10664	13018
Ensembl	ENSG00000102974	ENSMUSG00000005698
UniProt	P49711	Q61164
mRNA序列	NM_001191022	NM_181322
蛋白序列	NP_001177951	NP_851839
基因位置	Chr 16: 67.6 – 67.67 Mb	Chr 8: 105.64 – 105.68 Mb
PubMed查詢	[1]	[2]
閱 論 編

發現

CTCF最早被認為在雞體內抑制c-myc基因表現。CTCF蛋白和以CCCTC為核心序列的三個規則間隔重複蛋白相結合，故得名CCCTC結合因子^[5]。

功能

CTCF的主要功能是調控染色質的3D結構^[4]。CTCF和DNA雙鏈結合形成染色質環，並把DNA錨定在細胞結構上（例如核纖層）^[6]。此外，CTCF還能充當常染色質和異染色質的邊界。

DNA的3D結構會影響基因的調控，因此CTCF的活性會影響基因表現。絕緣子能阻礙強化子和啟動子的結合，而CTCF是絕緣子的主要活性部分^[5]。

已觀測到的活性

CTCF的結合有多種效應。目前尚不能確定下列功能是直接由CTCF導致。

轉錄調控

CTCF對於IGF2的抑制起重要作用。具體機制為CTCF和H19基因的基因銘印（ICR）區域、差異甲基化區域-1（DMR-1）和MAR3區域結合^[7]。

絕緣子

CTCF能通過和目標區域結合以阻礙強化子和啟動子的相互作用，從而降低強化子對某些功能域的調控能力^[8]。除此之外，CTCF還能作為染色質「路障」，阻止異染色質的進一步形成。

染色質結構調控

CTCF往往以二聚體的形式存在，這會導致DNA形成環狀結構。CTCF也經常在DNA和核纖層的結合處出現。使用ChIP-seq技術可以發現CTCF同黏連蛋白一起在基因組內廣泛存在，並對染色質的高級結構起調節作用^[9][10][11]。

RNA剪切調控

CTCF對mRNA剪切有調控作用^[12]。

與DNA結合

CTCF和共有序列CCGCGNGGNGGCAG相結合。這條序列在其結構域中有11個鋅指結構。CTCF和基因的結合被CpG的甲基化所影響^[13][14]。

CTCF在19個細胞系中大約有55000個共同的DNA結合位點（共77811個獨特位點）。CTCF能和不同的鋅指結構結合，這讓它的功能非常多樣化。大約有30000個CTCF的位點功能已經被定義。在人類的不同細胞中大約有15000-40000個CTCF結合位點。除此之外，高解析度的核小體比對現實CTCF的不同結合位點可能和核小體的定位有關^{[15][16][17][18]}。

蛋白互作

CTCF可能和Y box結合蛋白1有相互作用^[19]。黏連蛋白對CTCF形成的環狀結構有穩定作用^[20]。

參考

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衍生閱讀

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• Klenova EM, Morse HC, Ohlsson R, Lobanenkov VV. The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer. Semin. Cancer Biol. 2003, 12 (5): 399–414. PMID 12191639. doi:10.1016/S1044-579X(02)00060-3.
• Kuhn EJ, Geyer PK. Genomic insulators: connecting properties to mechanism. Curr. Opin. Cell Biol. 2004, 15 (3): 259–65. PMID 12787766. doi:10.1016/S0955-0674(03)00039-5.
• Recillas-Targa F, De La Rosa-Velázquez IA, Soto-Reyes E, Benítez-Bribiesca L. Epigenetic boundaries of tumour suppressor gene promoters: the CTCF connection and its role in carcinogenesis. J. Cell. Mol. Med. 2007, 10 (3): 554–68. PMID 16989720. doi:10.1111/j.1582-4934.2006.tb00420.x.
• Vostrov AA, Quitschke WW. The zinc finger protein CTCF binds to the APBbeta domain of the amyloid beta-protein precursor promoter. Evidence for a role in transcriptional activation. J. Biol. Chem. 1998, 272 (52): 33353–9. PMID 9407128. doi:10.1074/jbc.272.52.33353.
• Filippova GN, Lindblom A, Meincke LJ; et al. A widely expressed transcription factor with multiple DNA sequence specificity, CTCF, is localized at chromosome segment 16q22.1 within one of the smallest regions of overlap for common deletions in breast and prostate cancers. Genes Chromosomes Cancer. 1998, 22 (1): 26–36. PMID 9591631. doi:10.1002/(SICI)1098-2264(199805)22:1<26::AID-GCC4>3.0.CO;2-9. 引文格式1維護：顯式使用等標籤 (link)
• Bell AC, West AG, Felsenfeld G. The protein CTCF is required for the enhancer blocking activity of vertebrate insulators. Cell. 1999, 98 (3): 387–96. PMID 10458613. doi:10.1016/S0092-8674(00)81967-4.
• Pérez-Juste G, García-Silva S, Aranda A. An element in the region responsible for premature termination of transcription mediates repression of c-myc gene expression by thyroid hormone in neuroblastoma cells. J. Biol. Chem. 2000, 275 (2): 1307–14. PMID 10625678. doi:10.1074/jbc.275.2.1307.
• Lutz M, Burke LJ, Barreto G; et al. Transcriptional repression by the insulator protein CTCF involves histone deacetylases. Nucleic Acids Res. 2000, 28 (8): 1707–13. PMC 102824 . PMID 10734189. doi:10.1093/nar/28.8.1707. 引文格式1維護：顯式使用等標籤 (link)
• Bell AC, Felsenfeld G. Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature. 2000, 405 (6785): 482–5. PMID 10839546. doi:10.1038/35013100.
• Hark AT, Schoenherr CJ, Katz DJ; et al. CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. Nature. 2000, 405 (6785): 486–9. PMID 10839547. doi:10.1038/35013106. 引文格式1維護：顯式使用等標籤 (link)
• Chernukhin IV, Shamsuddin S, Robinson AF; et al. Physical and functional interaction between two pluripotent proteins, the Y-box DNA/RNA-binding factor, YB-1, and the multivalent zinc finger factor, CTCF. J. Biol. Chem. 2000, 275 (38): 29915–21. PMID 10906122. doi:10.1074/jbc.M001538200. 引文格式1維護：顯式使用等標籤 (link)
• Chao W, Huynh KD, Spencer RJ; et al. CTCF, a candidate trans-acting factor for X-inactivation choice. Science. 2002, 295 (5553): 345–7. PMID 11743158. doi:10.1126/science.1065982. 引文格式1維護：顯式使用等標籤 (link)
• Dintilhac A, Bernués J. HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences. J. Biol. Chem. 2002, 277 (9): 7021–8. PMID 11748221. doi:10.1074/jbc.M108417200.
• Filippova GN, Qi CF, Ulmer JE; et al. Tumor-associated zinc finger mutations in the CTCF transcription factor selectively alter tts DNA-binding specificity. Cancer Res. 2002, 62 (1): 48–52. PMID 11782357. 引文格式1維護：顯式使用等標籤 (link)
• Jia L, Young MF, Powell J; et al. Gene expression profile of human bone marrow stromal cells: high-throughput expressed sequence tag sequencing analysis. Genomics. 2002, 79 (1): 7–17. PMID 11827452. doi:10.1006/geno.2001.6683. 引文格式1維護：顯式使用等標籤 (link)
• Kanduri M, Kanduri C, Mariano P; et al. Multiple nucleosome positioning sites regulate the CTCF-mediated insulator function of the H19 imprinting control region. Mol. Cell. Biol. 2002, 22 (10): 3339–44. PMC 133793 . PMID 11971967. doi:10.1128/MCB.22.10.3339-3344.2002. 引文格式1維護：顯式使用等標籤 (link)
• Farrell CM, West AG, Felsenfeld G. Conserved CTCF insulator elements flank the mouse and human beta-globin loci. Mol. Cell. Biol. 2002, 22 (11): 3820–31. PMC 133827 . PMID 11997516. doi:10.1128/MCB.22.11.3820-3831.2002.