CTCF

位於16號人類染色體的基因

转录阻抑物CTCF,也被称为11锌指蛋白或CCCTC结合因子,是由人类CTCF基因编码的转录因子[1][2]。CTCF参与多个细胞进程,包括转录调控、绝缘子活性调控、V(D)J重组、染色质结构调控等[3][4]

CCCTC-结合因子(锌指蛋白)
PDB rendering based on 1x6h.
有效结构
PDB 直系同源检索:PDBe, RCSB
标识
代号 CTCF
扩展标识 遗传学604167 鼠基因109447 同源基因4786 GeneCards: CTCF Gene
RNA表达模式
更多表达数据
直系同源体
物种 人类 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查询 [1] [2]

发现

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CTCF最早被认为在鸡体内抑制c-myc基因表达。CTCF蛋白和以CCCTC为核心序列的三个规则间隔重复蛋白相结合,故得名CCCTC结合因子[5]

功能

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CTCF的主要功能是调控染色质的3D结构[4]。CTCF和DNA双链结合形成染色质环,并把DNA锚定在细胞结构上(例如核纤层)[6]。此外,CTCF还能充当常染色质和异染色质的边界。

DNA的3D结构会影响基因的调控,因此CTCF的活性会影响基因表达。绝缘子能阻碍增强子和启动子的结合,而CTCF是绝缘子的主要活性部分[5]

已观测到的活性

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CTCF的结合有多种效应。目前尚不能确定下列功能是直接由CTCF导致。

转录调控

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CTCF对于IGF2的抑制起重要作用。具体机制为CTCF和H19基因的基因铭印(ICR)区域、差异甲基化区域-1(DMR-1)和MAR3区域结合[7]

绝缘子

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CTCF能通过和目标区域结合以阻碍增强子和启动子的相互作用,从而降低增强子对某些功能域的调控能力[8]。除此之外,CTCF还能作为染色质“路障”,阻止异染色质的进一步形成。

染色质结构调控

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CTCF往往以二聚体的形式存在,这会导致DNA形成环状结构。CTCF也经常在DNA和核纤层的结合处出现。使用ChIP-seq技术可以发现CTCF同黏连蛋白一起在基因组内广泛存在,并对染色质的高级结构起调节作用[9][10][11]

RNA剪切调控

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CTCF对mRNA剪切有调控作用[12]

与DNA结合

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CTCF和共有序列CCGCGNGGNGGCAG相结合。这条序列在其结构域中有11个锌指结构。CTCF和基因的结合被CpG的甲基化所影响[13][14]

CTCF在19个细胞系中大约有55000个共同的DNA结合位点(共77811个独特位点)。CTCF能和不同的锌指结构结合,这让它的功能非常多样化。大约有30000个CTCF的位点功能已经被定义。在人类的不同细胞中大约有15000-40000个CTCF结合位点。除此之外,高分辨率的核小体比对现实CTCF的不同结合位点可能和核小体的定位有关[15][16][17][18]

蛋白互作

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CTCF可能和Y box结合蛋白1有相互作用[19]。黏连蛋白对CTCF形成的环状结构有稳定作用[20]

参考

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  1. ^ 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. (原始内容存档于2018-10-02). 
  2. ^ 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. (原始内容存档于2018-10-02). 
  3. ^ 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. (原始内容存档于2018-10-02). 
  4. ^ 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. (原始内容存档于2018-10-02). 
  5. ^ 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. (原始内容存档于2018-10-02). 
  6. ^ 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. (原始内容存档于2018-10-02). 
  7. ^ 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. (原始内容存档于2018-10-02). 
  8. ^ 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. (原始内容存档于2018-10-02). 
  9. ^ 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. (原始内容存档于2018-10-02). 
  10. ^ 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. (原始内容存档于2018-10-02). 
  11. ^ 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. (原始内容存档于2018-10-02). 
  12. ^ 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. (原始内容存档于2018-10-02). 
  13. ^ 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. (原始内容存档于2018-10-02). 
  14. ^ 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. (原始内容存档于2018-10-02). 
  15. ^ 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. (原始内容存档于2018-10-02). 
  16. ^ 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. (原始内容存档于2018-10-02). 
  17. ^ 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. (原始内容存档于2018-10-02). 
  18. ^ 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. (原始内容存档于2018-10-02). 
  19. ^ 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. (原始内容存档于2018-10-02). 
  20. ^ 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. (原始内容存档于2018-10-02). 

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