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Gene Review

Dnase1  -  deoxyribonuclease I

Mus musculus

Synonyms: AI788650, DNase I, DNaseI, Deoxyribonuclease I, Deoxyribonuclease-1, ...
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Disease relevance of Dnase1

  • Histopathology of lupus-like nephritis in Dnase1-deficient mice in comparison to NZB/W F1 mice [1].
  • METHODS: Dnase1-deficient and normal mice (both groups n = 10) underwent MRI with a body weight adapted dose of MS-325 on a 1.5 T whole body scanner equipped with a dedicated surface coil [2].
  • The developmental and subset-specific expression of the CD8 genes is under the control of a complex array of regulatory elements distributed along the locus and characterized by DNaseI hypersensitivity [3].
  • SJL lymphomas expressed the Ikaros isoform Ik6 that was absent in normal B cells. vSAg29+ cells exhibited increased DNaseI accessibility to chromatin at the vSAg29 initiation site [4].
  • The principal cap sites, which we assume to be transcriptional initiation points, are included in a DNaseI hypersensitive region of polyoma virus chromatin (4) [5].

High impact information on Dnase1

  • No qualitative differences in the DNaseI-footprints were detected when hormone-free receptor was compared to the hormone-receptor complex or even receptor complexed with the hormone antagonist RU486 [6].
  • Here we describe the phenotype of mice in which hypersensitive sites 1 and 2 (HSS1 and 2) of DNaseI hypersensitive Cluster II (CII), which are located upstream of the CD8 alpha gene, were deleted by targeted homologous recombination of the endogenous locus [3].
  • Xite harbors intergenic transcription start sites and DNaseI hypersensitive sites with allelic differences [7].
  • By using DNaseI footprinting and gel mobility shift assays we were able to show that two of these regions bind the erythroid specific nuclear factor NF-E1 (and ubiquitous factors) [8].
  • To assess possible alterations of c-myc transcriptional control in murine B-cell tumors, we have investigated the pattern of DNaseI hypersensitive sites in the gene's putative regulatory region and within the gene in a variety of genomic contexts [9].

Chemical compound and disease context of Dnase1


Biological context of Dnase1

  • Mapping of the murine Dnase1 gene locus to chromosome 16A1-3 did not coincide with one of the reported susceptibility loci in the NZB/W F1 model, although a reduced Dnasel serum and urine activity has been described previously in these mice [1].
  • Hepatic histopathology was performed, and biochemical parameters for APAP metabolism and necrosis were investigated, including depletion of glutathione/glutathione-disulfide (GSH+GSSG), beta-nicotinamide adenine dinucleotide (NADH+NAD+), and adenosine triphosphate (ATP); release of aminotransferases and Dnase1; and occurrence of DNA fragmentation [13].
  • Now we re-examined the DNASE1 gene expression pattern by taking advantage of the Dnase1 knockout mouse model [14].
  • Since Dnase1 knockout mice with the 129xC57Bl/6 mixed genetic background have indicated the protection against an anti-DNA autoimmune response as a new physiological function of Dnase1, knowledge of the physiological sites of its synthesis might prove helpful to find new therapeutic strategies [14].
  • The E2 enhancer accounts for most circadian transcriptional drive of the mPer2 locus by CLOCK:BMAL1, is a major site of DNaseI hypersensitivity in this region, and is constitutively bound by a transcriptional complex containing the CLOCK protein [15].

Anatomical context of Dnase1


Associations of Dnase1 with chemical compounds


Physical interactions of Dnase1


Regulatory relationships of Dnase1

  • In this study, we analyzed the participation of the hepatic endonuclease deoxyribonuclease 1 (DNASE1) during APAP-induced hepatotoxicity by employing a Dnase1 knockout (KO) mouse model [13].
  • By using an allele-specific general DNaseI sensitivity assay we show that there is preferential digestion of the expressed allele at sites within the transcribed locus but not in flanking sites located up to 70 kb 5'. A putative proximal boundary for the Xist domain is located within 10 kb upstream of promoter P1 [25].

Other interactions of Dnase1

  • An analysis of DNaseI hypersensitivity of a putative promoter of U2af1-rs1 showed an open chromatin conformation only on the unmethylated, expressed paternal allele [26].
  • The LCR is composed of a series of 5 DNaseI hypersensitive sites (5'HSs) that form in the nucleus of erythroid precursors [27].
  • Located centrally between Igf2 and H19 are two prominent DNaseI hypersensitive sites, and two stretches of sequence that are conserved between mouse and human [28].
  • Compared to the mouse promoter, the human promoter is missing a Sp1 cluster within a 310-bp upstream segment, and has AP-1, Oct-1 and two RORalpha sites that are protected from DNaseI by selected nuclear extracts [29].
  • Nuclei were digested with different concentrations of DNaseI and the extracted DNA was further cleaved by PstI and analyzed by Southern hybridization with DIG-labeled 695-bp AR promoter [22].

Analytical, diagnostic and therapeutic context of Dnase1


  1. Histopathology of lupus-like nephritis in Dnase1-deficient mice in comparison to NZB/W F1 mice. Jacob, M., Napirei, M., Ricken, A., Dixkens, C., Mannherz, H.G. Lupus (2002) [Pubmed]
  2. Contrast-enhanced magnetic resonance imaging (MS-325) in a murine model of systemic lupus erythematosus. Herborn, C.U., Waldschuetz, R., Lauenstein, T.C., Goyen, M., Lauffer, R.B., Moeroey, T., Debatin, J.F., Ruehm, S.G. Investigative radiology. (2002) [Pubmed]
  3. Variegated expression of CD8 alpha resulting from in situ deletion of regulatory sequences. Garefalaki, A., Coles, M., Hirschberg, S., Mavria, G., Norton, T., Hostert, A., Kioussis, D. Immunity (2002) [Pubmed]
  4. Regulation of mouse mammary tumor virus env transcriptional activator initiated mammary tumor virus superantigen transcripts in lymphomas of SJL/J mice: role of Ikaros, demethylation, and chromatin structural change in the transcriptional activation of mammary tumor virus superantigen. Thomas, R.M., Haleem, K., Siddique, A.B., Simmons, W.J., Sen, N., Zhang, D.J., Tsiagbe, V.K. J. Immunol. (2003) [Pubmed]
  5. Sequences at the capped 5'-ends of polyoma virus late region mRNAs: an example of extreme terminal heterogeneity. Cowie, A., Tyndall, C., Kamen, R. Nucleic Acids Res. (1981) [Pubmed]
  6. Steroid-free glucocorticoid receptor binds specifically to mouse mammary tumour virus DNA. Willmann, T., Beato, M. Nature (1986) [Pubmed]
  7. Xite, X-inactivation intergenic transcription elements that regulate the probability of choice. Ogawa, Y., Lee, J.T. Mol. Cell (2003) [Pubmed]
  8. The human beta-globin promoter; nuclear protein factors and erythroid specific induction of transcription. deBoer, E., Antoniou, M., Mignotte, V., Wall, L., Grosveld, F. EMBO J. (1988) [Pubmed]
  9. Chromatin structure of the murine c-myc locus: implications for the regulation of normal and chromosomally translocated genes. Fahrlander, P.D., Piechaczyk, M., Marcu, K.B. EMBO J. (1985) [Pubmed]
  10. Specific binding of progesterone receptor to progesterone-responsive elements does not require prior dimerization. Cohen-Solal, K., Bailly, A., Rauch, C., Quesne, M., Milgrom, E. Eur. J. Biochem. (1993) [Pubmed]
  11. Preferential binding of adriamycin and nogalamycin to DNase-I hypersensitive sites of Sarcoma-180 chromatin. Panda, C.K., Choudhury, K., Neogy, R.K. Chem. Biol. Interact. (1986) [Pubmed]
  12. Homeostatic Effects of TLR9 Signaling in Experimental Colitis. Lee, J., Rachmilewitz, D., Raz, E. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  13. Deoxyribonuclease 1 aggravates acetaminophen-induced liver necrosis in male CD-1 mice. Napirei, M., Basnakian, A.G., Apostolov, E.O., Mannherz, H.G. Hepatology (2006) [Pubmed]
  14. Expression pattern of the deoxyribonuclease 1 gene: lessons from the Dnase1 knockout mouse. Napirei, M., Ricken, A., Eulitz, D., Knoop, H., Mannherz, H.G. Biochem. J. (2004) [Pubmed]
  15. A noncanonical E-box enhancer drives mouse Period2 circadian oscillations in vivo. Yoo, S.H., Ko, C.H., Lowrey, P.L., Buhr, E.D., Song, E.J., Chang, S., Yoo, O.J., Yamazaki, S., Lee, C., Takahashi, J.S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  16. Identifying gene regulatory elements by genomic microarray mapping of DNaseI hypersensitive sites. Follows, G.A., Dhami, P., G??ttgens, B., Bruce, A.W., Campbell, P.J., Dillon, S.C., Smith, A.M., Koch, C., Donaldson, I.J., Scott, M.A., Dunham, I., Janes, M.E., Vetrie, D., Green, A.R. Genome Res. (2006) [Pubmed]
  17. Macrophages ingest and are activated by bacterial DNA. Stacey, K.J., Sweet, M.J., Hume, D.A. J. Immunol. (1996) [Pubmed]
  18. Parental chromosome-specific chromatin conformation in the imprinted U2af1-rs1 gene in the mouse. Feil, R., Boyano, M.D., Allen, N.D., Kelsey, G. J. Biol. Chem. (1997) [Pubmed]
  19. Tissue-specific and hormonal regulation of calbindin-D9K fusion genes in transgenic mice. Romagnolo, B., Cluzeaud, F., Lambert, M., Colnot, S., Porteu, A., Molina, T., Tomasset, M., Vandewalle, A., Kahn, A., Perret, C. J. Biol. Chem. (1996) [Pubmed]
  20. Deoxyribonuclease I-like III is an inducible macrophage barrier to liposomal transfection. Wilber, A., Lu, M., Schneider, M.C. Mol. Ther. (2002) [Pubmed]
  21. Chromatin structure and imprinting: developmental control of DNase-I sensitivity in the mouse insulin-like growth factor 2 gene. Feil, R., Handel, M.A., Allen, N.D., Reik, W. Dev. Genet. (1995) [Pubmed]
  22. Sex steroids reduce DNaseI accessibility of androgen receptor promoter in adult male mice brain. Kumar, R.C., Thakur, M.K. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  23. Bax is a transcriptional target and mediator of c-myc-induced apoptosis. Mitchell, K.O., Ricci, M.S., Miyashita, T., Dicker, D.T., Jin, Z., Reed, J.C., El-Deiry, W.S. Cancer Res. (2000) [Pubmed]
  24. Protein factors in thyrotropic tumor nuclear extracts bind to a region of the mouse thyrotropin beta-subunit promoter essential for expression in thyrotropes. Wood, W.M., Ocran, K.W., Kao, M.Y., Gordon, D.F., Alexander, L.M., Gutierrez-Hartmann, A., Ridgway, E.C. Mol. Endocrinol. (1990) [Pubmed]
  25. Chromatin structure analysis of the mouse Xist locus. McCabe, V., Formstone, E.J., O'Neill, L.P., Turner, B.M., Brockdorff, N. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  26. Inactive allele-specific methylation and chromatin structure of the imprinted gene U2af1-rs1 on mouse chromosome 11. Shibata, H., Yoshino, K., Sunahara, S., Gondo, Y., Katsuki, M., Ueda, T., Kamiya, M., Muramatsu, M., Murakami, Y., Kalcheva, I., Plass, C., Chapman, V.M., Hayashizaki, Y. Genomics (1996) [Pubmed]
  27. Targeted deletion of 5'HS1 and 5'HS4 of the beta-globin locus control region reveals additive activity of the DNaseI hypersensitive sites. Bender, M.A., Roach, J.N., Halow, J., Close, J., Alami, R., Bouhassira, E.E., Groudine, M., Fiering, S.N. Blood (2001) [Pubmed]
  28. A skeletal muscle-specific mouse Igf2 repressor lies 40 kb downstream of the gene. Ainscough, J.F., John, R.M., Barton, S.C., Surani, M.A. Development (2000) [Pubmed]
  29. Isolation and characterization of the human prosaposin promoter. Sun, Y., Jin, P., Witte, D.P., Grabowski, G.A. Gene (1998) [Pubmed]
  30. Features of systemic lupus erythematosus in Dnase1-deficient mice. Napirei, M., Karsunky, H., Zevnik, B., Stephan, H., Mannherz, H.G., Möröy, T. Nat. Genet. (2000) [Pubmed]
  31. Cell type-specific gene expression in the neuroendocrine system. A neuroendocrine-specific regulatory element in the promoter of chromogranin A, a ubiquitous secretory granule core protein. Wu, H., Rozansky, D.J., Webster, N.J., O'Connor, D.T. J. Clin. Invest. (1994) [Pubmed]
  32. Quantification of DNaseI-sensitivity by real-time PCR: quantitative analysis of DNaseI-hypersensitivity of the mouse beta-globin LCR. McArthur, M., Gerum, S., Stamatoyannopoulos, G. J. Mol. Biol. (2001) [Pubmed]
  33. TBX5, a gene mutated in Holt-Oram syndrome, is regulated through a GC box and T-box binding elements (TBEs). Sun, G., Lewis, L.E., Huang, X., Nguyen, Q., Price, C., Huang, T. J. Cell. Biochem. (2004) [Pubmed]
  34. Nucleoproteins derived from subnuclear RNA polymerase complexes of metastatic large-cell lymphoma cells possess transcription activities and regulatory properties in vitro. Rosenberg-Nicolson, N.L., Nicolson, G.L. J. Cell. Biochem. (1992) [Pubmed]
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