CTCF
![本頁使用了標題或全文手工轉換](http://upload.wikimedia.org/wikipedia/commons/thumb/c/cd/Zh_conversion_icon_m.svg/35px-Zh_conversion_icon_m.svg.png)
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]。
發現
[編輯]CTCF最早被認為在雞體內抑制c-myc基因表達。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
[編輯]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達。絕緣子能阻礙增強子和啟動子的結合,而CTCF是絕緣子的主要活性部分[5]。
已觀測到的活性
[編輯]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
[編輯]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
[編輯]CTCF能通過和目標區域結合以阻礙增強子和啟動子的相互作用,從而降低增強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
[編輯]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
[編輯]CTCF對mRNA剪切有調控作用[12]。
與DNA結合
[編輯]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,高解像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
[編輯]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
[編輯]- ^ Malik, V. S.; Reusser, F. Restriction enzyme map for streptomycete plasmid pUC3. Plasmid. 1979-10, 2 (4): 627–631 [2018-10-01]. ISSN 0147-619X. PMID 231272. (原始內容存檔於2018-10-02).
- ^ Zuccato, E.; Mussini, E.; Spignoli, G.; Pupita, F. Evidence of a lack of enteric side-effects induced by DEAE-dextran in man. Pharmacological Research Communications. 1987-8, 19 (8): 547–553 [2018-10-01]. ISSN 0031-6989. PMID 2448833. (原始內容存檔於2018-10-02).
- ^ Ishikawa, H. [Effect of anesthetized antral mucosa on anti-peristaltic discharge]. Nihon Heikatsukin Gakkai Zasshi. 1987-4, 23 (2): 115–124 [2018-10-01]. ISSN 0374-3527. PMID 3444155. (原始內容存檔於2018-10-02).
- ^ 4.0 4.1 Dahlgren, C. Difference in extracellular radical release after chemotactic factor and calcium ionophore activation of the oxygen radical-generating system in human neutrophils. Biochimica Et Biophysica Acta. 1987-08-19, 930 (1): 33–38 [2018-10-01]. ISSN 0006-3002. PMID 3040116. (原始內容存檔於2018-10-02).
- ^ 5.0 5.1 Lobanenkov, V. V.; Nicolas, R. H.; Adler, V. V.; Paterson, H.; Klenova, E. M.; Polotskaja, A. V.; Goodwin, G. H. A novel sequence-specific DNA binding protein which interacts with three regularly spaced direct repeats of the CCCTC-motif in the 5'-flanking sequence of the chicken c-myc gene. Oncogene. 1990-12, 5 (12): 1743–1753 [2018-10-01]. ISSN 0950-9232. PMID 2284094. (原始內容存檔於2018-10-02).
- ^ Guelen, Lars; Pagie, Ludo; Brasset, Emilie; Meuleman, Wouter; Faza, Marius B.; Talhout, Wendy; Eussen, Bert H.; de Klein, Annelies; Wessels, Lodewyk. Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature. 2008-06-12, 453 (7197): 948–951 [2018-10-01]. ISSN 1476-4687. PMID 18463634. doi:10.1038/nature06947. (原始內容存檔於2018-10-02).
- ^ Dunn, Katherine L.; Davie, James R. The many roles of the transcriptional regulator CTCF. Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire. 2003-6, 81 (3): 161–167 [2018-10-01]. ISSN 0829-8211. PMID 12897849. doi:10.1139/o03-052. (原始內容存檔於2018-10-02).
- ^ Malyshev, Iu I.; Iarygin, A. S.; Malyshev, M. Iu. [Surgical correction of multivalvular defects in patients who had earlier undergone heart surgery]. Grudnaia Khirurgiia (Moscow, Russia). 1989-11, (6): 17–20 [2018-10-01]. ISSN 0017-4866. PMID 2612964. (原始內容存檔於2018-10-02).
- ^ Yusufzai, Timur M.; Tagami, Hideaki; Nakatani, Yoshihiro; Felsenfeld, Gary. CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species. Molecular Cell. 2004-01-30, 13 (2): 291–298 [2018-10-01]. ISSN 1097-2765. PMID 14759373. (原始內容存檔於2018-10-02).
- ^ Hou, Chunhui; Zhao, Hui; Tanimoto, Keiji; Dean, Ann. CTCF-dependent enhancer-blocking by alternative chromatin loop formation. Proceedings of the National Academy of Sciences of the United States of America. 2008-12-23, 105 (51): 20398–20403 [2018-10-01]. ISSN 1091-6490. PMC 2629272
. PMID 19074263. doi:10.1073/pnas.0808506106. (原始內容存檔於2018-10-02).
- ^ Johnson, E. K.; Kardong, K. V.; Mackessy, S. P. Electric shocks are ineffective in treatment of lethal effects of rattlesnake envenomation in mice. Toxicon: Official Journal of the International Society on Toxinology. 1987, 25 (12): 1347–1349 [2018-10-01]. ISSN 0041-0101. PMID 3438923. (原始內容存檔於2018-10-02).
- ^ Shukla, Sanjeev; Kavak, Ersen; Gregory, Melissa; Imashimizu, Masahiko; Shutinoski, Bojan; Kashlev, Mikhail; Oberdoerffer, Philipp; Sandberg, Rickard; Oberdoerffer, Shalini. CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing. Nature. 2011-11-03, 479 (7371): 74–79 [2018-10-01]. ISSN 1476-4687. PMID 21964334. doi:10.1038/nature10442. (原始內容存檔於2018-10-02).
- ^ Kroeker, L. [Nursing--a new future]. Krankenpflege (Frankfurt Am Main, Germany). 1989-9, 43 (9): 426–429 [2018-10-01]. ISSN 0944-9183. PMID 2572726. (原始內容存檔於2018-10-02).
- ^ Bell, A. C.; Felsenfeld, G. Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature. 2000-05-25, 405 (6785): 482–485 [2018-10-01]. ISSN 0028-0836. PMID 10839546. doi:10.1038/35013100. (原始內容存檔於2018-10-02).
- ^ Gomoliako, I. V. [Morphological diagnosis of chronic bronchitis in patients with tuberculosis of the lungs]. Problemy Tuberkuleza. 1991, (4): 64–68 [2018-10-01]. ISSN 0032-9533. PMID 1852749. (原始內容存檔於2018-10-02).
- ^ Reiher, H.; Peschke, G.; May, G.; Göbel, U.; Randow, H. [Severe impalement injury with primary surgical, gynecologic and urologic management]. Zentralblatt Fur Chirurgie. 1990, 115 (16): 1041–1043 [2018-10-01]. ISSN 0044-409X. PMID 2238977. (原始內容存檔於2018-10-02).
- ^ Suzuki, S. S.; Smith, G. K. Spontaneous EEG spikes in the normal hippocampus. II. Relations to synchronous burst discharges. Electroencephalography and Clinical Neurophysiology. 1988-6, 69 (6): 532–540 [2018-10-01]. ISSN 0013-4694. PMID 2453330. (原始內容存檔於2018-10-02).
- ^ Teif, Vladimir B.; Vainshtein, Yevhen; Caudron-Herger, Maïwen; Mallm, Jan-Philipp; Marth, Caroline; Höfer, Thomas; Rippe, Karsten. Genome-wide nucleosome positioning during embryonic stem cell development. Nature Structural & Molecular Biology. 2012-11, 19 (11): 1185–1192 [2018-10-01]. ISSN 1545-9985. PMID 23085715. doi:10.1038/nsmb.2419. (原始內容存檔於2018-10-02).
- ^ Chernukhin, I. V.; Shamsuddin, S.; Robinson, A. F.; Carne, A. F.; Paul, A.; El-Kady, A. I.; Lobanenkov, V. V.; Klenova, E. M. Physical and functional interaction between two pluripotent proteins, the Y-box DNA/RNA-binding factor, YB-1, and the multivalent zinc finger factor, CTCF. The Journal of Biological Chemistry. 2000-09-22, 275 (38): 29915–29921 [2018-10-01]. ISSN 0021-9258. PMID 10906122. doi:10.1074/jbc.M001538200. (原始內容存檔於2018-10-02).
- ^ Kagey, Michael H.; Newman, Jamie J.; Bilodeau, Steve; Zhan, Ye; Orlando, David A.; van Berkum, Nynke L.; Ebmeier, Christopher C.; Goossens, Jesse; Rahl, Peter B. Mediator and cohesin connect gene expression and chromatin architecture. Nature. 2010-09-23, 467 (7314): 430–435 [2018-10-01]. ISSN 1476-4687. PMC 2953795
. PMID 20720539. doi:10.1038/nature09380. (原始內容存檔於2018-10-02).
衍生閱讀
[編輯]- Ohlsson R, Renkawitz R, Lobanenkov V. CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease. Trends Genet. 2001, 17 (9): 520–7. PMID 11525835. doi:10.1016/S0168-9525(01)02366-6.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
|