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Gene Review

F8a  -  factor 8-associated gene A

Mus musculus

Synonyms: AI852759, CpG island protein, DXUcsf1, F8a1, Factor VIII intron 22 protein
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Disease relevance of F8a


Psychiatry related information on F8a


High impact information on F8a


Chemical compound and disease context of F8a


Biological context of F8a


Anatomical context of F8a

  • Hypermethylation of a CpG island in the noncoding exon 1 was associated with silencing of this gene in malignant B cells [16].
  • It was found that HpaII site H-7 in the CpG island of the X-chromosome-linked Pgk-1 gene is less than or equal to 10% methylated in oocytes and male embryos but becomes 40% methylated in female embryos at 6.5 days; about the time of X-chromosome inactivation of the inner cell mass [17].
  • We have found that this CpG island includes a novel intronic promoter that is active in embryonic and germ cells [18].
  • In the mouse preimplantation embryo, most genes are unmethylated but a wave of de novo methylation prior to gastrulation generates a bimodal pattern characterized by unmethylated CpG island-containing housekeeping genes and fully modified tissue-specific genes [19].
  • The CpG island-like pVHCk plasmid containing the bacterial chloramphenicol acyltransferase (CAT) gene under the control of SV40 early promoter was transfected in L929 mouse fibroblast cells [20].

Associations of F8a with chemical compounds


Physical interactions of F8a


Regulatory relationships of F8a


Other interactions of F8a

  • Lambda G28, a mouse genomic clone homologous to the human P3 gene and associated with a CpG island, also hybridizes to human probes for the neighboring GdX gene [28].
  • We show that a CpG island associated with Gatm is unmethylated, as is a large CpG island associated with a neighboring gene [29].
  • These findings show a link between inactivation of the pRb pathway and induction of DNA hypermethylation of CpG island-containing genes in tumorigenesis [30].
  • Here we describe a novel gene, Enox (expressed neighbor of Xist), that maps to an unmethylated CpG island 10 kb upstream of Xist [31].
  • Because there is a 283-bp CpG island region in the HO-1 promoter, we hypothesized that methylation of the island is responsible for the age-related HO-1 down-regulation in the cortex [32].

Analytical, diagnostic and therapeutic context of F8a

  • Gene silencing by CpG island promoter hypermethylation has awakened the interest for DNA demethylating agents as chemotherapy drugs [33].
  • In this method, referred to as CpG-selected and amplified binding, fragments derived from the CpG island fraction of the murine genome are selected by a gel mobility shift assay using in vitro-transcribed and -translated RXR-RAR [24].
  • Methylation status was assessed using regular and quantitative methylation-specific PCR and the CpG island was found to be hypomethylated at all ages [32].
  • Using pulsed field gel electrophoresis and Southern hybridization, we determined the approximate location of each probe with respect to the CpG island in both the DM and the chromosome [34].
  • Analysis of the 5' upstream region by DNA sequencing and Southern blotting suggested that it contained a CpG island, and a major site of transcription initiation 201 bp upstream of the translation start site was found by RNase protection and primer extension [35].


  1. The tumour suppressor RASSF1A regulates mitosis by inhibiting the APC-Cdc20 complex. Song, M.S., Song, S.J., Ayad, N.G., Chang, J.S., Lee, J.H., Hong, H.K., Lee, H., Choi, N., Kim, J., Kim, H., Kim, J.W., Choi, E.J., Kirschner, M.W., Lim, D.S. Nat. Cell Biol. (2004) [Pubmed]
  2. CpG island protects Rous sarcoma virus-derived vectors integrated into nonpermissive cells from DNA methylation and transcriptional suppression. Hejnar, J., Hájková, P., Plachy, J., Elleder, D., Stepanets, V., Svoboda, J. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  3. A novel homeodomain-encoding gene is associated with a large CpG island interrupted by the myotonic dystrophy unstable (CTG)n repeat. Boucher, C.A., King, S.K., Carey, N., Krahe, R., Winchester, C.L., Rahman, S., Creavin, T., Meghji, P., Bailey, M.E., Chartier, F.L. Hum. Mol. Genet. (1995) [Pubmed]
  4. Complete genetic suppression of polyp formation and reduction of CpG-island hypermethylation in Apc(Min/+) Dnmt1-hypomorphic Mice. Eads, C.A., Nickel, A.E., Laird, P.W. Cancer Res. (2002) [Pubmed]
  5. Biology of the fragile X mental retardation protein, an RNA-binding protein. Khandjian, E.W. Biochem. Cell Biol. (1999) [Pubmed]
  6. Deficiency of Mbd2 suppresses intestinal tumorigenesis. Sansom, O.J., Berger, J., Bishop, S.M., Hendrich, B., Bird, A., Clarke, A.R. Nat. Genet. (2003) [Pubmed]
  7. Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease. Tufarelli, C., Stanley, J.A., Garrick, D., Sharpe, J.A., Ayyub, H., Wood, W.G., Higgs, D.R. Nat. Genet. (2003) [Pubmed]
  8. High levels of de novo methylation and altered chromatin structure at CpG islands in cell lines. Antequera, F., Boyes, J., Bird, A. Cell (1990) [Pubmed]
  9. Imprinted expression of the Igf2r gene depends on an intronic CpG island. Wutz, A., Smrzka, O.W., Schweifer, N., Schellander, K., Wagner, E.F., Barlow, D.P. Nature (1997) [Pubmed]
  10. Demethylation of CpG islands in embryonic cells. Frank, D., Keshet, I., Shani, M., Levine, A., Razin, A., Cedar, H. Nature (1991) [Pubmed]
  11. Role of human ribosomal RNA (rRNA) promoter methylation and of methyl-CpG-binding protein MBD2 in the suppression of rRNA gene expression. Ghoshal, K., Majumder, S., Datta, J., Motiwala, T., Bai, S., Sharma, S.M., Frankel, W., Jacob, S.T. J. Biol. Chem. (2004) [Pubmed]
  12. Molecular and functional analysis of the utrophin promoter. Dennis, C.L., Tinsley, J.M., Deconinck, A.E., Davies, K.E. Nucleic Acids Res. (1996) [Pubmed]
  13. Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. Macleod, D., Charlton, J., Mullins, J., Bird, A.P. Genes Dev. (1994) [Pubmed]
  14. Parental imprinting: potentially active chromatin of the repressed maternal allele of the mouse insulin-like growth factor II (Igf2) gene. Sasaki, H., Jones, P.A., Chaillet, J.R., Ferguson-Smith, A.C., Barton, S.C., Reik, W., Surani, M.A. Genes Dev. (1992) [Pubmed]
  15. Methylation-dependent gene silencing induced by interleukin 1beta via nitric oxide production. Hmadcha, A., Bedoya, F.J., Sobrino, F., Pintado, E. J. Exp. Med. (1999) [Pubmed]
  16. The IL-12Rbeta2 gene functions as a tumor suppressor in human B cell malignancies. Airoldi, I., Di Carlo, E., Banelli, B., Moserle, L., Cocco, C., Pezzolo, A., Sorrentino, C., Rossi, E., Romani, M., Amadori, A., Pistoia, V. J. Clin. Invest. (2004) [Pubmed]
  17. Use of a HpaII-polymerase chain reaction assay to study DNA methylation in the Pgk-1 CpG island of mouse embryos at the time of X-chromosome inactivation. Singer-Sam, J., Grant, M., LeBon, J.M., Okuyama, K., Chapman, V., Monk, M., Riggs, A.D. Mol. Cell. Biol. (1990) [Pubmed]
  18. An alternative promoter in the mouse major histocompatibility complex class II I-Abeta gene: implications for the origin of CpG islands. Macleod, D., Ali, R.R., Bird, A. Mol. Cell. Biol. (1998) [Pubmed]
  19. Dynamics of DNA methylation during development. Brandeis, M., Ariel, M., Cedar, H. Bioessays (1993) [Pubmed]
  20. Inhibition of poly(ADP-ribosyl)ation introduces an anomalous methylation pattern in transfected foreign DNA. Zardo, G., Marenzi, S., Perilli, M., Caiafa, P. FASEB J. (1999) [Pubmed]
  21. An epigenetic mouse model for molecular and behavioral neuropathologies related to schizophrenia vulnerability. Tremolizzo, L., Carboni, G., Ruzicka, W.B., Mitchell, C.P., Sugaya, I., Tueting, P., Sharma, R., Grayson, D.R., Costa, E., Guidotti, A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  22. Preselection of retrovirally transduced bone marrow avoids subsequent stem cell gene silencing and age-dependent extinction of expression of human beta-globin in engrafted mice. Kalberer, C.P., Pawliuk, R., Imren, S., Bachelot, T., Takekoshi, K.J., Fabry, M., Eaves, C.J., London, I.M., Humphries, R.K., Leboulch, P. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  23. Analysis of the mouse Dhfr/Rep-3 major promoter region by using linker-scanning and internal deletion mutations and DNase I footprinting. Smith, M.L., Mitchell, P.J., Crouse, G.F. Mol. Cell. Biol. (1990) [Pubmed]
  24. Isolation of a novel retinoic acid-responsive gene by selection of genomic fragments derived from CpG-island-enriched DNA. Shago, M., Giguére, V. Mol. Cell. Biol. (1996) [Pubmed]
  25. p53-mediated repression of DNA methyltransferase 1 expression by specific DNA binding. Peterson, E.J., Bögler, O., Taylor, S.M. Cancer Res. (2003) [Pubmed]
  26. Identification and characterization of the cell type-specific and developmentally regulated alpha7 integrin gene promoter. Ziober, B.L., Kramer, R.H. J. Biol. Chem. (1996) [Pubmed]
  27. The mouse CREB (cAMP responsive element binding protein) gene: structure, promoter analysis, and chromosomal localization. Cole, T.J., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Schütz, G., Ruppert, S. Genomics (1992) [Pubmed]
  28. Linkage and sequence conservation of the X-linked genes DXS253E (P3) and DXS254E (GdX) in mouse and man. Filippi, M., Tribioli, C., Toniolo, D. Genomics (1990) [Pubmed]
  29. Gatm, a creatine synthesis enzyme, is imprinted in mouse placenta. Sandell, L.L., Guan, X.J., Ingram, R., Tilghman, S.M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  30. Regulation of DNA methyltransferase 1 by the pRb/E2F1 pathway. McCabe, M.T., Davis, J.N., Day, M.L. Cancer Res. (2005) [Pubmed]
  31. Enox, a novel gene that maps 10 kb upstream of Xist and partially escapes X inactivation. Johnston, C.M., Newall, A.E., Brockdorff, N., Nesterova, T.B. Genomics (2002) [Pubmed]
  32. Expression and regulation of heme oxygenase isozymes in the developing mouse cortex. Zhao, H., Wong, R.J., Nguyen, X., Kalish, F., Mizobuchi, M., Vreman, H.J., Stevenson, D.K., Contag, C.H. Pediatr. Res. (2006) [Pubmed]
  33. The novel DNA methylation inhibitor zebularine is effective against the development of murine T-cell lymphoma. Herranz, M., Martín-Caballero, J., Fraga, M.F., Ruiz-Cabello, J., Flores, J.M., Desco, M., Marquez, V., Esteller, M. Blood (2006) [Pubmed]
  34. Chromosome breakpoints near CpG islands in double minutes. Foureman, P., Winfield, J.A., Hahn, P.J. Gene (1998) [Pubmed]
  35. Cloning and transcriptional analysis of the promoter of the human type 2 desmocollin gene (DSC2). Marsden, M.D., Collins, J.E., Greenwood, M.D., Adams, M.J., Fleming, T.P., Magee, A.I., Buxton, R.S. Gene (1997) [Pubmed]
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