CTCF

Short description: Transcription factor

Generic protein structure example

Transcriptional repressor CTCF also known as 11-zinc finger protein or CCCTC-binding factor is a transcription factor that in humans is encoded by the CTCF gene.[1][2] CTCF is involved in many cellular processes, including transcriptional regulation, insulator activity, V(D)J recombination[3] and regulation of chromatin architecture.[4]

## Contents

* 1 Discovery
* 2 Function
* 3 Evolution
* 4 Observed activity
* 4.1 Transcriptional regulation
* 4.2 Insulation
* 4.3 Regulation of chromatin architecture
* 4.4 Regulation of RNA splicing
* 5 DNA binding
* 6 Protein-protein interactions
* 7 References
* 8 Further reading
* 9 External links

## Discovery

CCCTC-Binding factor or CTCF was initially discovered as a negative regulator of the chicken c-myc gene. This protein was found to be binding to three regularly spaced repeats of the core sequence CCCTC and thus was named CCCTC binding factor.[5]

## Function

Although CTCF was initially discovered as a transcription factor,[5] more recent research has revealed its central role in regulating the 3D chromatin architecture.[6][7][8][4]

The role of CTCF in 3D chromatin architecture arises from its participation in the process of loop extrusion. Loop extrusion is a mechanism by which SMC complexes such as cohesin translocate along chromatin and progressively enlarge DNA loops[9][10]. In higher eukaryotes, CTCF acts as a directional barrier to extrusion: when cohesin encounters a DNA-bound CTCF oriented in the correct direction, extrusion halts. Through this mechanism, CTCF helps form chromatin loops between specific genomic elements, and establish the boundaries of topologically associating domains (TADs), thereby influencing long-range regulation of gene expression.

CTCF binding has also been both shown to promote and repress gene expression. It is unknown whether CTCF affects gene expression solely through its looping activity, or if it has some other, unknown, activity.[4] In addition to demarcating TADs, CTCF mediates promoter–enhancer interactions within a TAD.[11] It is likely that CTCF helps to bridge the transcription factors bound to transcription start sites and RNA polymerase. This model has been suggested in pioneering works on the beta-globin locus[12][4].

## Evolution

CTCF is conserved across eumetazoans, including cnidarians and bilaterians, but is absent from earlier-branching animals such as sponges and from non-animal eukaryotes, suggesting that it arose in the common ancestor of eumetazoans approximately 600–700 million years ago[13].

## Observed activity

The binding of CTCF has been shown to have many effects, which are enumerated below. In each case, it is unknown if CTCF directly evokes the outcome or if it does so indirectly (in particular through its looping role).

### Transcriptional regulation

The protein CTCF plays a heavy role in repressing the insulin-like growth factor 2 gene, by binding to the H-19 imprinting control region (ICR) along with differentially-methylated region-1 (DMR1) and MAR3.[14][15]

### Insulation

Binding of targeting sequence elements by CTCF can block the interaction between enhancers and promoters, therefore limiting the activity of enhancers to certain functional domains. Besides acting as enhancer blocking, CTCF can also act as a chromatin barrier[16] by preventing the spread of heterochromatin structures.

### Regulation of chromatin architecture

DNA loop extrusion through cohesin rings

CTCF plays a central role in organizing three-dimensional chromatin structure in eumetazoans by regulating the process of loop extrusion. In this mechanism, cohesin complexes translocate along chromatin and progressively enlarge DNA loops until they encounter DNA-bound CTCF. The role of CTCF as an extrusion barrier, and its function in establishing topologically associating domain (TAD) boundaries, was first proposed theoretically and later supported by experiments showing that depletion of CTCF disrupts these domain boundaries.

The barrier activity of CTCF is directional. Cohesin extrusion is halted when cohesin encounters a CTCF site in the appropriate orientation, which is determined by the orientation of the CTCF motif in the genome[17][18][19]. Structural and biochemical studies indicate that this directionality arises because the N-terminal region of CTCF interacts with cohesin and blocks its translocation along DNA.[20][21][22] Computer simulations suggests that when cohesin is halted at a CTCF site, it should continue extruding DNA from the opposite side[23]. This mechanism contributes to the formation of topologically associating domains (TADs) and other chromatin loops observed in genome-wide chromosome conformation capture experiments. Recent studies showed that such CTCF-CTCF loops are rather transient[24][25]. Stable CTCF-CTCF loops are not essential for formation of TADs, which instead arise due to continuous loop extrusion.

Through this barrier function, CTCF can both facilitate and restrict genomic interactions. CTCF sites positioned near regulatory elements can promote loop formation between them, whereas CTCF sites located between genomic regions can prevent their interaction and act as insulators[26][6][27][28]. In addition to its role as an extrusion barrier, some studies suggest that CTCF may also form homodimers[29], which may contribute to chromatin loop stabilization.

### Regulation of RNA splicing

CTCF binding has been shown to influence mRNA splicing.[30]

## DNA binding

CTCF binds to the consensus sequence RCCASNAGRKGGCRS (in IUPAC notation).[31][32][33] This sequence is defined by 11 zinc finger motifs in its structure. CTCF's binding is disrupted by CpG methylation of the DNA it binds to.[34] On the other hand, CTCF binding may set boundaries for the spreading of DNA methylation.[35] In recent studies, CTCF binding loss is reported to increase localized CpG methylation, which reflected another epigenetic remodeling role of CTCF in human genome.[36][37][38]

CTCF binds to an average of about 55,000 DNA sites in 19 diverse cell types (12 normal and 7 immortal) and in total 77,811 distinct binding sites across all 19 cell types.[39] CTCF's ability to bind to multiple sequences through the usage of various combinations of its zinc fingers earned it the status of a "multivalent protein".[1] More than 30,000 CTCF binding sites have been characterized.[40] The human genome contains anywhere between 15,000 and 40,000 CTCF binding sites depending on cell type, suggesting a widespread role for CTCF in gene regulation.[16][31][41] In addition CTCF binding sites act as nucleosome positioning anchors so that, when used to align various genomic signals, multiple flanking nucleosomes can be readily identified.[16][42] On the other hand, high-resolution nucleosome mapping studies have demonstrated that the differences of CTCF binding between cell types may be attributed to the differences in nucleosome locations.[43] Methylation loss at CTCF-binding site of some genes has been found to be related to human diseases, including male infertility.[32]

## Protein-protein interactions

CTCF binds to itself to form homodimers.[29] CTCF has also been shown to interact with Y box binding protein 1.[44] CTCF also co-localizes with cohesin, which extrudes chromatin loops by actively translocating one or two DNA strands through its ring-shaped structure, until it meets CTCF in a proper orientation.[45] CTCF is also known to interact with chromatin remodellers such as Chd4 and Snf2h (SMARCA5).[46]

## References

1. ↑ 1.0 1.1 "An exceptionally conserved transcriptional repressor, CTCF, employs different combinations of zinc fingers to bind diverged promoter sequences of avian and mammalian c-myc oncogenes". Mol. Cell. Biol. 16 (6): 2802–13. June 1996. doi:10.1128/mcb.16.6.2802. PMID 8649389.
2. ↑ "CTCF physically links cohesin to chromatin". Proc. Natl. Acad. Sci. U.S.A. 105 (24): 8309–14. June 2008. doi:10.1073/pnas.0801273105. PMID 18550811. Bibcode: 2008PNAS..105.8309R.
3. ↑ "The role of CTCF in regulating V(D)J recombination". Curr. Opin. Immunol. 24 (2): 153–9. April 2012. doi:10.1016/j.coi.2012.01.003. PMID 22424610.
4. ↑ 4.0 4.1 4.2 4.3 Phillips JE; Corces VG (June 2009). "CTCF: master weaver of the genome". Cell 137 (7): 1194–211. doi:10.1016/j.cell.2009.06.001. PMID 19563753. Bibcode: 2009Cell..137.1194P.
5. ↑ 5.0 5.1 "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 5 (12): 1743–53. December 1990. PMID 2284094.
6. ↑ 6.0 6.1 Nora, Elphège P.; Goloborodko, Anton; Valton, Anne-Laure; Gibcus, Johan H.; Uebersohn, Alec; Abdennur, Nezar; Dekker, Job; Mirny, Leonid A. et al. (May 2017). "Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization". Cell 169 (5): 930–944.e22. doi:10.1016/j.cell.2017.05.004. ISSN 0092-8674. PMID 28525758. Bibcode: 2017Cell..169..930N.
7. ↑ de Wit, Elzo; Vos, Erica S.M.; Holwerda, Sjoerd J.B.; Valdes-Quezada, Christian; Verstegen, Marjon J.A.M.; Teunissen, Hans; Splinter, Erik; Wijchers, Patrick J. et al. (November 2015). "CTCF Binding Polarity Determines Chromatin Looping". Molecular Cell 60 (4): 676–684. doi:10.1016/j.molcel.2015.09.023. ISSN 1097-2765. PMID 26527277. https://linkinghub.elsevier.com/retrieve/pii/S1097276515007625.
8. ↑ Wutz, Gordana; Várnai, Csilla; Nagasaka, Kota; Cisneros, David A.; Stocsits, Roman R.; Tang, Wen; Schoenfelder, Stefan; Jessberger, Gregor et al. (2017-12-01). "Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins" (in en). The EMBO Journal 36 (24): 3573–3599. doi:10.15252/embj.201798004. ISSN 1460-2075. PMID 29217591.
9. ↑ Davidson, Iain F.; Peters, Jan-Michael (July 2021). "Genome folding through loop extrusion by SMC complexes" (in en). Nature Reviews Molecular Cell Biology 22 (7): 445–464. doi:10.1038/s41580-021-00349-7. ISSN 1471-0080. PMID 33767413. https://www.nature.com/articles/s41580-021-00349-7.
10. ↑ Banigan, Edward J.; Mirny, Leonid A. (2020-06-01). "Loop extrusion: theory meets single-molecule experiments". Current Opinion in Cell Biology. Cell Nucleus 64: 124–138. doi:10.1016/j.ceb.2020.04.011. ISSN 0955-0674. PMID 32534241. https://www.sciencedirect.com/science/article/pii/S0955067420300570.
11. ↑ "p63 cooperates with CTCF to modulate chromatin architecture in skin keratinocytes". Epigenetics & Chromatin 12 (1). June 2019. doi:10.1186/s13072-019-0280-y. PMID 31164150.
12. ↑ Palstra, Robert-Jan; Tolhuis, Bas; Splinter, Erik; Nijmeijer, Rian; Grosveld, Frank; de Laat, Wouter (October 2003). "The β-globin nuclear compartment in development and erythroid differentiation" (in en). Nature Genetics 35 (2): 190–194. doi:10.1038/ng1244. ISSN 1546-1718. PMID 14517543. https://www.nature.com/articles/ng1244.
13. ↑ Heger, P.; Marin, B.; Bartkuhn, M.; Schierenberg, E.; Wiehe, T. (2012). "PNAS" (in en). Proceedings of the National Academy of Sciences of the United States of America 109 (43): 17507–17512. doi:10.1073/pnas.1111941109. PMID 23045651.
14. ↑ "CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease". Trends Genet. 17 (9): 520–7. 2001. doi:10.1016/S0168-9525(01)02366-6. PMID 11525835.
15. ↑ "The many roles of the transcriptional regulator CTCF". Biochem. Cell Biol. 81 (3): 161–7. 2003. doi:10.1139/o03-052. PMID 12897849. Bibcode: 2003BCB....81..161D.
16. ↑ 16.0 16.1 16.2 "Global analysis of the insulator binding protein CTCF in chromatin barrier regions reveals demarcation of active and repressive domains". Genome Res. 19 (1): 24–32. 2009. doi:10.1101/gr.082800.108. PMID 19056695.
17. ↑ de Wit, Elzo; Vos, Erica S.M.; Holwerda, Sjoerd J.B.; Valdes-Quezada, Christian; Verstegen, Marjon J.A.M.; Teunissen, Hans; Splinter, Erik; Wijchers, Patrick J. et al. (November 2015). "CTCF Binding Polarity Determines Chromatin Looping". Molecular Cell 60 (4): 676–684. doi:10.1016/j.molcel.2015.09.023. ISSN 1097-2765. PMID 26527277. https://linkinghub.elsevier.com/retrieve/pii/S1097276515007625.
18. ↑ Guo, Ya; Xu, Quan; Canzio, Daniele; Shou, Jia; Li, Jinhuan; Gorkin, David U.; Jung, Inkyung; Wu, Haiyang et al. (August 2015). "CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function". Cell 162 (4): 900–910. doi:10.1016/j.cell.2015.07.038. ISSN 0092-8674. PMID 26276636.
19. ↑ Zhang, Hongshan; Shi, Zhubing; Banigan, Edward J.; Kim, Yoori; Yu, Hongtao; Bai, Xiao-chen; Finkelstein, Ilya J. (August 2023). "CTCF and R-loops are boundaries of cohesin-mediated DNA looping". Molecular Cell 83 (16): 2856–2871.e8. doi:10.1016/j.molcel.2023.07.006. ISSN 1097-2765. PMID 37536339. https://linkinghub.elsevier.com/retrieve/pii/S1097276523005208.
20. ↑ Pugacheva, E. M.; Kubo, N.; Loukinov, D.; Tajmul, M.; Kang, S.; Kovalchuk, A. L.; Strunnikov, A. V.; Zentner, G. E. et al. (2020). "PNAS" (in en). Proceedings of the National Academy of Sciences of the United States of America 117 (4): 2020–2031. doi:10.1073/pnas.1911708117. PMID 31937660.
21. ↑ Li, Yan; Haarhuis, Judith H. I.; Sedeño Cacciatore, Ángela; Oldenkamp, Roel; van Ruiten, Marjon S.; Willems, Laureen; Teunissen, Hans; Muir, Kyle W. et al. (February 2020). "The structural basis for cohesin–CTCF-anchored loops" (in en). Nature 578 (7795): 472–476. doi:10.1038/s41586-019-1910-z. ISSN 1476-4687. PMID 31905366. Bibcode: 2020Natur.578..472L.
22. ↑ Nora, Elphège P.; Caccianini, Laura; Fudenberg, Geoffrey; So, Kevin; Kameswaran, Vasumathi; Nagle, Abigail; Uebersohn, Alec; Hajj, Bassam et al. (2020-11-05). "Molecular basis of CTCF binding polarity in genome folding" (in en). Nature Communications 11 (1): 5612. doi:10.1038/s41467-020-19283-x. ISSN 2041-1723. PMID 33154377. Bibcode: 2020NatCo..11.5612N.
23. ↑ Fudenberg, Geoffrey; Imakaev, Maxim; Lu, Carolyn; Goloborodko, Anton; Abdennur, Nezar; Mirny, Leonid A. (May 2016). "Formation of Chromosomal Domains by Loop Extrusion". Cell Reports 15 (9): 2038–2049. doi:10.1016/j.celrep.2016.04.085. ISSN 2211-1247. PMID 27210764. Bibcode: 2016CellR..15.2038F.
24. ↑ Gabriele, M.; Brandão, H. B.; Grosse-Holz, S.; Jha, A.; Dailey, G. M.; Cattoglio, C.; Hsieh, T. S.; Mirny, L. et al. (2022). "Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging" (in en). Science 376 (6592): 496–501. doi:10.1126/science.abn6583. PMID 35420890. PMC 9069445. Bibcode: 2022Sci...376..496G. https://www.science.org/action/cookieAbsent. Retrieved 2026-03-11.
25. ↑ Mach, Pia; Kos, Pavel I.; Zhan, Yinxiu; Cramard, Julie; Gaudin, Simon; Tünnermann, Jana; Marchi, Edoardo; Eglinger, Jan et al. (December 2022). "Cohesin and CTCF control the dynamics of chromosome folding" (in en). Nature Genetics 54 (12): 1907–1918. doi:10.1038/s41588-022-01232-7. ISSN 1546-1718. PMID 36471076.
26. ↑ Hnisz, D.; Weintraub, A. S.; Day, D. S.; Valton, A. L.; Bak, R. O.; Li, C. H.; Goldmann, J.; Lajoie, B. R. et al. (2016). "Activation of proto-oncogenes by disruption of chromosome neighborhoods" (in en). Science 351 (6280): 1454–1458. doi:10.1126/science.aad9024. PMID 26940867. PMC 4884612. Bibcode: 2016Sci...351.1454H. https://www.science.org/action/cookieAbsent. Retrieved 2026-03-11.
27. ↑ Rittenhouse, Natalie L; Dowen, Jill M (2024-04-01). "Cohesin regulation and roles in chromosome structure and function". Current Opinion in Genetics & Development 85. doi:10.1016/j.gde.2024.102159. ISSN 0959-437X. PMID 38382406.
28. ↑ Kubo, Naoki; Ishii, Haruhiko; Xiong, Xiong; Bianco, Simona; Meitinger, Franz; Hu, Rong; Hocker, James D.; Conte, Mattia et al. (February 2021). "Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation" (in en). Nature Structural & Molecular Biology 28 (2): 152–161. doi:10.1038/s41594-020-00539-5. ISSN 1545-9985. PMID 33398174.
29. ↑ 29.0 29.1 "CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species". Mol. Cell 13 (2): 291–8. January 2004. doi:10.1016/S1097-2765(04)00029-2. PMID 14759373.
30. ↑ "CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing". Nature 479 (7371): 74–9. November 2011. doi:10.1038/nature10442. PMID 21964334. PMC 7398428. Bibcode: 2011Natur.479...74S. https://zenodo.org/record/1233317.
31. ↑ 31.0 31.1 "Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome". Cell 128 (6): 1231–45. March 2007. doi:10.1016/j.cell.2006.12.048. PMID 17382889.
32. ↑ 32.0 32.1 "Methylation loss at H19 imprinted gene correlates with methylenetetrahydrofolate reductase gene promoter hypermethylation in semen samples from infertile males". Epigenetics 8 (9): 990–7. September 2013. doi:10.4161/epi.25798. PMID 23975186.
33. ↑ "CTCF binding site classes exhibit distinct evolutionary, genomic, epigenomic and transcriptomic features". Genome Biology 10 (11). 2009-11-18. doi:10.1186/gb-2009-10-11-r131. PMID 19922652.
34. ↑ "Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene". Nature 405 (6785): 482–5. May 2000. doi:10.1038/35013100. PMID 10839546. Bibcode: 2000Natur.405..482B.
35. ↑ "DNA de-methylation in embryonic stem cells controls CTCF-dependent chromatin boundaries". Genome Research 29 (5): 750–61. May 2019. doi:10.1101/gr.239707.118. PMID 30948436.
36. ↑ "Novel role of prostate cancer risk variant rs7247241 on PPP1R14A isoform transition through allelic TF binding and CpG methylation". Human Molecular Genetics 31 (10): 1610–1621. May 2022. doi:10.1093/hmg/ddab347. PMID 34849858.
37. ↑ "CTCF loss mediates unique DNA hypermethylation landscapes in human cancers". Clinical Epigenetics 12 (1). June 2020. doi:10.1186/s13148-020-00869-7. PMID 32503656.
38. ↑ "CTCF haploinsufficiency destabilizes DNA methylation and predisposes to cancer". Cell Reports 7 (4): 1020–1029. May 2014. doi:10.1016/j.celrep.2014.04.004. PMID 24794443.
39. ↑ "Widespread plasticity in CTCF occupancy linked to DNA methylation". Genome Res. 22 (9): 1680–8. September 2012. doi:10.1101/gr.136101.111. PMID 22955980.
40. ↑ "CTCFBSDB: a CTCF-binding site database for characterization of vertebrate genomic insulators". Nucleic Acids Res. 36 (Database issue): D83–7. January 2008. doi:10.1093/nar/gkm875. PMID 17981843.
41. ↑ "Systematic discovery of regulatory motifs in conserved regions of the human genome, including thousands of CTCF insulator sites". Proc. Natl. Acad. Sci. U.S.A. 104 (17): 7145–50. 2007. doi:10.1073/pnas.0701811104. PMID 17442748. Bibcode: 2007PNAS..104.7145X.
42. ↑ "The insulator binding protein CTCF positions 20 nucleosomes around its binding sites across the human genome". PLOS Genetics 4 (7). 2008. doi:10.1371/journal.pgen.1000138. PMID 18654629.
43. ↑ "Genome-wide nucleosome positioning during embryonic stem cell development". Nat Struct Mol Biol 19 (11): 1185–92. 2012. doi:10.1038/nsmb.2419. PMID 23085715.
44. ↑ "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. 275 (38): 29915–21. September 2000. doi:10.1074/jbc.M001538200. PMID 10906122.
45. ↑ Kagey MH; Newman JJ; Bilodeau S; Zhan Y; Orlando DA; van Berkum NL; Ebmeier CC; Goossens J et al. (September 2010). "Mediator and cohesin connect gene expression and chromatin architecture". Nature 467 (7314): 430–5. doi:10.1038/nature09380. PMID 20720539. Bibcode: 2010Natur.467..430K.
46. ↑ "CTCF-dependent chromatin boundaries formed by asymmetric nucleosome arrays with decreased linker length". Nucleic Acids Research 47 (21): 11181–11196. September 2019. doi:10.1093/nar/gkz908. PMID 31665434.

## Further reading

* "CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease". Trends Genet. 17 (9): 520–7. 2001. doi:10.1016/S0168-9525(01)02366-6. PMID 11525835.
* "The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer". Semin. Cancer Biol. 12 (5): 399–414. 2003. doi:10.1016/S1044-579X(02)00060-3. PMID 12191639.
* "Genomic insulators: connecting properties to mechanism". Curr. Opin. Cell Biol. 15 (3): 259–65. 2004. doi:10.1016/S0955-0674(03)00039-5. PMID 12787766.
* "Epigenetic boundaries of tumour suppressor gene promoters: the CTCF connection and its role in carcinogenesis". J. Cell. Mol. Med. 10 (3): 554–68. 2007. doi:10.1111/j.1582-4934.2006.tb00420.x. PMID 16989720.
* "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. 272 (52): 33353–9. 1998. doi:10.1074/jbc.272.52.33353. PMID 9407128.
* "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 22 (1): 26–36. 1998. doi:10.1002/(SICI)1098-2264(199805)22:1<26::AID-GCC4>3.0.CO;2-9. PMID 9591631.
* "The protein CTCF is required for the enhancer blocking activity of vertebrate insulators". Cell 98 (3): 387–96. 1999. doi:10.1016/S0092-8674(00)81967-4. PMID 10458613.
* "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. 275 (2): 1307–14. 2000. doi:10.1074/jbc.275.2.1307. PMID 10625678.
* "Transcriptional repression by the insulator protein CTCF involves histone deacetylases". Nucleic Acids Res. 28 (8): 1707–13. 2000. doi:10.1093/nar/28.8.1707. PMID 10734189.
* "Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene". Nature 405 (6785): 482–5. 2000. doi:10.1038/35013100. PMID 10839546. Bibcode: 2000Natur.405..482B.
* "CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus". Nature 405 (6785): 486–9. 2000. doi:10.1038/35013106. PMID 10839547. Bibcode: 2000Natur.405..486H.
* "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. 275 (38): 29915–21. 2000. doi:10.1074/jbc.M001538200. PMID 10906122.
* "CTCF, a candidate trans-acting factor for X-inactivation choice". Science 295 (5553): 345–7. 2002. doi:10.1126/science.1065982. PMID 11743158.
* "HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences". J. Biol. Chem. 277 (9): 7021–8. 2002. doi:10.1074/jbc.M108417200. PMID 11748221. https://digital.csic.es/bitstream/10261/112516/4/jbc.M108417200.full.pdf.
* "Tumor-associated zinc finger mutations in the CTCF transcription factor selectively alter tts DNA-binding specificity". Cancer Res. 62 (1): 48–52. 2002. PMID 11782357.
* "Multiple nucleosome positioning sites regulate the CTCF-mediated insulator function of the H19 imprinting control region". Mol. Cell. Biol. 22 (10): 3339–44. 2002. doi:10.1128/MCB.22.10.3339-3344.2002. PMID 11971967.
* "Conserved CTCF insulator elements flank the mouse and human beta-globin loci". Mol. Cell. Biol. 22 (11): 3820–31. 2002. doi:10.1128/MCB.22.11.3820-3831.2002. PMID 11997516.

## External links

* CCCTC-binding+factor at the US National Library of Medicine Medical Subject Headings (MeSH)
* FactorBook CTCF
* Human CTCF genome location and CTCF gene details page in the UCSC Genome Browser.
* https://www.ctcfemory.com/ A Group for families affected by CTCF mutations

* v
* t
* e

PDB gallery

* 1x6h: Solution structures of the C2H2 type zinc finger domain of human Transcriptional repressor CTCF

* 2ct1: Solution Structure of the zinc finger domain of Transcriptional repressor CTCF protein

* v
* t
* e

Transcription factors and intracellular receptors

(1) Basic domains

| (1.1) Basic leucine zipper (bZIP)|

* Activating transcription factor
* AATF
* 1
* 2
* 3
* 4
* 5
* 6
* 7
* AP-1
* c-Fos
* FOSB
* FOSL1
* FOSL2
* JDP2
* c-Jun
* JUNB
* JunD
* BACH
* 1
* 2
* BATF
* BLZF1
* C/EBP
* α
* β
* γ
* δ
* ε
* ζ
* CREB
* 1
* 3
* L1
* CREM
* DBP
* DDIT3
* GABPA
* GCN4
* HLF
* MAF
* B
* F
* G
* K
* NFE
* 2
* L1
* L2
* L3
* NFIL3
* NRL
* NRF
* 1
* 2
* 3
* Biology:XBP1

|

(1.2) Basic helix-loop-helix (bHLH)|

* ATOH1
* AhR
* AHRR
* ARNT
* ASCL1
* BHLH
* 2
* 3
* 9
* ARNTL
* ARNTL
* ARNTL2
* Biology:CLOCK
* EPAS1
* FIGLA
* HAND
* 1
* 2
* HES
* 5
* 6
* HEY
* 1
* 2
* L
* HES1
* HIF
* 1A
* 3A
* ID
* 1
* 2
* 3
* 4
* LYL1
* MESP2
* MXD4
* MYCL1
* MYCN
* Myogenic regulatory factors
* MyoD
* Myogenin
* MYF5
* MYF6
* Biology:Neurogenins
* 1
* 2
* 3
* NeuroD
* 1
* 2
* NPAS
* 1
* 2
* 3
* OLIG
* 1
* 2
* Pho4
* Scleraxis
* SIM
* 1
* 2
* TAL
* 1
* 2
* Twist
* USF1

(1.3) bHLH-ZIP|

* AP-4
* MAX
* Biology:MXD1
* MXD3
* MITF
* MNT
* MLX
* MLXIPL
* MXI1
* Myc
* SREBP
* 1
* 2

(1.4) NF-1|

* NFI
* A
* B
* C
* X
* SMAD
* R-SMAD
* 1
* 2
* 3
* 5
* 9
* I-SMAD
* 6
* 7
* 4)

(1.5) RF-X|

* RFX
* 1
* 2
* 3
* 4
* 5
* 6
* ANK

(1.6) Basic helix-span-helix (bHSH)|

* AP-2
* α
* β
* γ
* δ
* ε

(2) Zinc finger DNA-binding domains

| (2.1) Nuclear receptor (Cys4)|

| subfamily 1|

* Thyroid hormone
* α
* β
* CAR
* FXR
* LXR
* α
* β
* PPAR
* α
* β/δ
* γ
* PXR
* RAR
* α
* β
* γ
* ROR
* α
* β
* γ
* Rev-ErbA
* α
* β
* VDR

|

subfamily 2|

* COUP-TF
* (I
* II
* Ear-2
* HNF4
* α
* γ
* PNR
* RXR
* α
* β
* γ
* Testicular receptor
* 2
* 4
* TLX

subfamily 3|

* Steroid hormone
* Androgen
* Estrogen
* α
* β
* Glucocorticoid
* Mineralocorticoid
* Progesterone
* Estrogen related
* α
* β
* γ

subfamily 4|

* NUR
* NGFIB
* NOR1
* NURR1

subfamily 5|

* LRH-1
* SF1

subfamily 6|

* GCNF

subfamily 0|

* DAX1
* SHP

(2.2) Other Cys4|

* GATA
* 1
* 2
* 3
* 4
* 5
* 6
* MTA
* 1
* 2
* 3
* TRPS1

(2.3) Cys2His2|

* General transcription factors
* TFIIA
* TFIIB
* TFIID
* TFIIE
* 1
* 2
* TFIIF
* 1
* 2
* TFIIH
* 1
* 2
* 4
* 2I
* 3A
* 3C1
* 3C2

* ATBF1
* BCL
* 6
* 11A
* 11B
* CTCF
* E4F1
* EGR
* 1
* 2
* 3
* 4
* ERV3
* GFI1
* GLI-Krüppel family
* 1
* 2
* 3
* REST
* S1
* S2
* YY1
* HIC
* 1
* 2
* HIVEP
* 1
* 2
* 3
* IKZF
* 1
* 2
* 3
* ILF
* 2
* 3
* KLF
* 1
* 2
* 3
* 4
* 5
* 6
* 7
* 8
* 9
* 10
* 11
* 12
* 13
* 14
* 15
* 17
* MTF1
* MYT1
* OSR1
* PRDM9
* SALL
* 1
* 2
* 3
* 4
* SP
* 1
* 2
* 4
* 7
* 8
* Biology:TSHZ3
* WT1
* Zbtb7
* 7A
* 7B
* ZBTB
* 11
* 16
* 17
* 20
* 32
* 33
* 40
* zinc finger
* 3
* 7
* 9
* 10
* 19
* 22
* 24
* 33B
* 34
* 35
* 41
* 43
* 44
* 51
* 74
* 143
* 146
* 148
* 165
* 202
* 217
* 219
* 238
* 239
* 259
* 267
* 268
* 281
* 295
* 300
* 318
* 330
* 346
* 350
* 365
* 366
* 384
* 423
* 451
* 452
* 471
* 593
* 638
* 644
* 649
* 655

(2.4) Cys6|

* HIVEP1

(2.5) Alternating composition|

* AIRE
* DIDO1
* GRLF1
* ING
* 1
* 2
* 4
* JARID
* 1A
* 1B
* 1C
* 1D
* 2
* JMJD1B

(2.6) WRKY|

* WRKY

(3) Helix-turn-helix domains

| (3.1) Homeodomain|

* ARX
* CDX
* 1
* 2
* CRX
* CUTL1
* DBX
* 1
* 2
* DLX
* 1
* 2
* 3
* 4
* 5
* 6
* EMX
* 1
* 2
* EN
* 1
* 2
* FHL
* 1
* 2
* 3
* HESX1
* HHEX
* HLX
* Homeobox
* A1
* A2
* A3
* A4
* A5
* A7
* A9
* A10
* A11
* A13
* B1
* B2
* B3
* B4
* B5
* B6
* B7
* B8
* B9
* B13
* C4
* C5
* C6
* C8
* C9
* C10
* C11
* C12
* C13
* D1
* D3
* D4
* D8
* D9
* D10
* D11
* D12
* D13
* HOPX
* IRX
* 1
* 2
* 3
* 4
* 5
* 6
* MKX
* LMX
* 1A
* 1B
* MEIS
* 1
* 2
* MEOX2
* MNX1
* MSX
* 1
* 2
* NANOG
* NKX
* 2-1
* 2-2
* 2-3
* 2-5
* 3-1
* 3-2
* 6-1
* 6-2
* NOBOX
* PBX
* 1
* 2
* 3
* PHF
* 1
* 3
* 6
* 8
* 10
* 16
* 17
* 20
* 21A
* PHOX
* 2A
* 2B
* PITX
* 1
* 2
* 3
* POU domain
* PIT-1
* BRN-3: A
* B
* C
* Octamer transcription factor: 1
* 2
* 3/4
* 6
* 7
* 11
* OTX
* 1
* 2
* PDX1
* SATB2
* SHOX2
* SIX
* 1
* 2
* 3
* 4
* 5
* VAX1
* ZEB
* 1
* 2

|

(3.2) Paired box|

* PAX
* 1
* 2
* 3
* 4
* 5
* 6
* 7
* 8
* 9
* PRRX
* 1
* 2
* RAX

(3.3) Fork head / winged helix|

* E2F
* 1
* 2
* 3
* 4
* 5
* FOX proteins
* A1
* A2
* A3
* C1
* C2
* D3
* D4
* E1
* E3
* F1
* G1
* H1
* I1
* J1
* J2
* K1
* K2
* L2
* M1
* N1
* N3
* O1
* O3
* O4
* P1
* P2
* P3
* P4

(3.4) Heat shock factors|

* HSF
* 1
* 2
* 4

(3.5) Tryptophan clusters|

* ELF
* 2
* 4
* 5
* EGF
* ELK
* 1
* 3
* 4
* ERF
* ETS
* 1
* 2
* ERG
* SPIB
* ETV
* 1
* 4
* 5
* 6
* FLI1
* Interferon regulatory factors
* 1
* 2
* 3
* 4
* 5
* 6
* 7
* 8
* MYB
* MYBL2

(3.6) TEA domain|

* transcriptional enhancer factor
* 1
* 2
* 3
* 4

(4) β-Scaffold factors with minor groove contacts

| (4.1) Rel homology region|

* NF-κB
* NFKB1
* NFKB2
* REL
* RELA
* RELB
* NFAT
* C1
* C2
* C3
* C4
* 5

|

(4.2) STAT|

* STAT
* 1
* 2
* 3
* 4
* 5
* 6

(4.3) p53|

* p53
* TBX
* 1
* 2
* 3
* 5
* 19
* 21
* 22
* TBR1
* TBR2
* TFT
* MYRF
* Biology:TP63

(4.4) MADS box|

* Mef2
* A
* B
* C
* D
* SRF

(4.6) TATA-binding proteins|

* TBP
* TBPL1

(4.7) High-mobility group|

* BBX
* HMGB
* 1
* 2
* 3
* 4
* HMGN
* 1
* 2
* 3
* 4
* HNF
* 1A
* 1B
* LEF1
* SOX
* 1
* 2
* 3
* 4
* 5
* 6
* 8
* 9
* 10
* 11
* 12
* 13
* 14
* 15
* 18
* 21
* SRY
* SSRP1
* TCF
* 3
* 4
* TOX
* 1
* 2
* 3
* 4

(4.9) Grainyhead|

* TFCP2

(4.10) Cold-shock domain|

* CSDA
* YBX1

(4.11) Runt|

* CBF
* CBFA2T2
* CBFA2T3
* RUNX1
* RUNX2
* RUNX3
* RUNX1T1

(0) Other transcription factors

| (0.2) HMGI(Y)|

* HMGA
* 1
* 2
* HBP1

|

(0.3) Pocket domain|

* Rb
* RBL1
* RBL2

(0.5) AP-2/EREBP-related factors|

* Apetala 2
* EREBP
* B3

(0.6) Miscellaneous|

* ARID
* 1A
* 1B
* 2
* 3A
* 3B
* 4A
* CAP
* IFI
* 16
* 35
* MLL
* 2
* 3
* T1
* MNDA
* NFY
* A
* B
* C
* Rho/Sigma

see also transcription factor/coregulator deficiencies

0.00

(0 votes)

Original source: https://en.wikipedia.org/wiki/CTCF. Read more

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