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Gene Review

Cigs1  -  conserved intergenic sequence 1

Mus musculus

Synonyms: CNS-1, Cns1, HSS1, HSS2
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Disease relevance of Cigs1

  • Il4 gene accessibility, analyzed by restriction enzyme accessibility (REA) at sites in the promoter, in the second intron (DNase I hypersensitivity sites HSII and HSIII) and in CNS-1 in the two populations was also similar [1].
  • We demonstrate that treatment with hsFlt3L leads to inhibition of tumor growth and significantly increased life span of animals implanted with syngeneic CNS-1 glioma cells [2].
  • Conservation of CNS1 and exclusion of its role in atopic eczema susceptibility [3].
  • These include a CCAAT box at HSS2, a novel brain-specific footprint near an adenovirus promoter element E2aE-C beta and a single liver-specific footprint associated with an POU/octamer binding site at HSS4 [4].

High impact information on Cigs1

  • Thus, monoallelism at the Il4 locus is a complex process; expression is linked to opening CNS1 but probability of expression is controlled at other sites [5].
  • 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 [6].
  • Conserved noncoding sequence elements longer than 80 bp with >/=75% nucleotide sequence identity comprise approximately 1% of the genomic sequence in this region [7].
  • Cns-1 transcripts are expressed in differentiating cells cultured from the early postnatal cerebellum [8].
  • The NMDA-induced increase in Cns-1 mRNA was reduced by pretreatment with calcium chelators EGTA or 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) tetrakis(acetoxymethyl) [8].

Chemical compound and disease context of Cigs1

  • Mimosine-treated neural precursor cells injected into established intracerebral CNS-1 gliomas in nude mice migrated extensively throughout the tumor and into the surrounding parenchyma beyond the tumor over 3 days [9].

Biological context of Cigs1

  • However, the replication timing of this locus is consistently early during S phase in both Th1 and Th2 cells under either the wild-type or CNS-1 deletion background [10].
  • These studies suggest that specific activation of the NMDA receptor in cultures of differentiating cerebellar cells increases Cns-1 gene expression and that calcium entry through the NMDA channel may be required for this response [8].
  • The sequences associated with hypersensitive site 1 (HSS1) represented the principal area of homology within which three conserved subdomains were apparent: area I (-2694 to -2561 base pairs (bp)), area II (-2139 to -1958 bp), and area III (-1879 to -1799 bp) [11].
  • The human Iglambda enhancer consists of three separated sequence elements that we identified previously by mapping DNase I-hypersensitive regions (HSS) downstream of the C region of the Iglambda L chain genes (HSS-1, HSS-2, and HSS-3) [12].
  • Three DNase I-hypersensitive sites (HSS0, HSS1 and HSS2) have been described upstream of the rabbit WAP gene in the lactating mammary gland and correspond to important regulatory regions [13].

Anatomical context of Cigs1


Associations of Cigs1 with chemical compounds

  • Mimosine-treated neural precursor cells, infected with rRp450 and injected into intracerebral CNS-1 tumors, also migrated within the tumor with the appearance of foci of HSV-thymidine kinase-positive (TK+) cells, presumably including tumor cells, distributed throughout the tumor and in the surrounding parenchyma over a similar period [9].

Other interactions of Cigs1


Analytical, diagnostic and therapeutic context of Cigs1

  • NMDA receptor activation in differentiating cerebellar cell cultures regulates the expression of a new POU gene, Cns-1 [8].
  • In addition, by chromatin immunoprecipitation assay, we show that GR is rapidly recruited to endogenous CNS-1 chromatin after GC stimulation [18].
  • CpG-ODNs had no effect on a s.c. CNS1 tumor in nude mice, which suggested that CpG-ODN is not directly cytotoxic and that immunostimulation is required for the antitumoral effect [19].
  • Gel mobility shift assays revealed a similar but not identical banding pattern with brain and liver nuclear extracts at HSS2, and HSS3, however the banding pattern for HSS4 was predominantly brain-specific [4].


  1. Probabilistic regulation of IL-4 production in Th2 cells: accessibility at the Il4 locus. Guo, L., Hu-Li, J., Paul, W.E. Immunity (2004) [Pubmed]
  2. Inflammatory and anti-glioma effects of an adenovirus expressing human soluble Fms-like tyrosine kinase 3 ligand (hsFlt3L): treatment with hsFlt3L inhibits intracranial glioma progression. Ali, S., Curtin, J.F., Zirger, J.M., Xiong, W., King, G.D., Barcia, C., Liu, C., Puntel, M., Goverdhana, S., Lowenstein, P.R., Castro, M.G. Mol. Ther. (2004) [Pubmed]
  3. Conservation of CNS1 and exclusion of its role in atopic eczema susceptibility. Elliott, K.S., Anney, R.J., Fitzpatrick, E.B., Williamson, R., Forrest, S.M. J. Allergy Clin. Immunol. (2002) [Pubmed]
  4. Characterization of DNase I hypersensitive sites in the mouse 68-kDa neurofilament gene. Kure, R., Ivanov, T.R., Brown, I.R. Neurochem. Res. (1996) [Pubmed]
  5. Probabilistic regulation in TH2 cells accounts for monoallelic expression of IL-4 and IL-13. Guo, L., Hu-Li, J., Paul, W.E. Immunity (2005) [Pubmed]
  6. 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]
  7. Comparative sequence of human and mouse BAC clones from the mnd2 region of chromosome 2p13. Jang, W., Hua, A., Spilson, S.V., Miller, W., Roe, B.A., Meisler, M.H. Genome Res. (1999) [Pubmed]
  8. NMDA receptor activation in differentiating cerebellar cell cultures regulates the expression of a new POU gene, Cns-1. Bulleit, R.F., Cui, H., Wang, J., Lin, X. J. Neurosci. (1994) [Pubmed]
  9. Neural precursor cells for delivery of replication-conditional HSV-1 vectors to intracerebral gliomas. Herrlinger, U., Woiciechowski, C., Sena-Esteves, M., Aboody, K.S., Jacobs, A.H., Rainov, N.G., Snyder, E.Y., Breakefield, X.O. Mol. Ther. (2000) [Pubmed]
  10. Replication initiation from a novel origin identified in the th2 cytokine cluster locus requires a distant conserved noncoding sequence. Hayashida, T., Oda, M., Ohsawa, K., Yamaguchi, A., Hosozawa, T., Locksley, R.M., Giacca, M., Masai, H., Miyatake, S. J. Immunol. (2006) [Pubmed]
  11. Pancreatic beta cell-specific transcription of the pdx-1 gene. The role of conserved upstream control regions and their hepatic nuclear factor 3beta sites. Gerrish, K., Gannon, M., Shih, D., Henderson, E., Stoffel, M., Wright, C.V., Stein, R. J. Biol. Chem. (2000) [Pubmed]
  12. Regulation of human Ig lambda light chain gene expression by NF-kappa B. Combriato, G., Klobeck, H.G. J. Immunol. (2002) [Pubmed]
  13. Hormone-induced modifications of the chromatin structure surrounding upstream regulatory regions conserved between the mouse and rabbit whey acidic protein genes. Millot, B., Montoliu, L., Fontaine, M.L., Mata, T., Devinoy, E. Biochem. J. (2003) [Pubmed]
  14. Deletion of a coordinate regulator of type 2 cytokine expression in mice. Mohrs, M., Blankespoor, C.M., Wang, Z.E., Loots, G.G., Afzal, V., Hadeiba, H., Shinkai, K., Rubin, E.M., Locksley, R.M. Nat. Immunol. (2001) [Pubmed]
  15. Identification of two evolutionarily conserved and functional regulatory elements in intron 2 of the human BRCA1 gene. Wardrop, S.L., Brown, M.A. Genomics (2005) [Pubmed]
  16. Basal chromatin modification at the IL-4 gene in helper T cells. Grogan, J.L., Wang, Z.E., Stanley, S., Harmon, B., Loots, G.G., Rubin, E.M., Locksley, R.M. J. Immunol. (2003) [Pubmed]
  17. Characterization of a human multilineage-colony-stimulating factor cDNA clone identified by a conserved noncoding sequence in mouse interleukin-3. Dorssers, L., Burger, H., Bot, F., Delwel, R., Geurts van Kessel, A.H., Löwenberg, B., Wagemaker, G. Gene (1987) [Pubmed]
  18. Transcriptional regulation of the mouse IL-7 receptor alpha promoter by glucocorticoid receptor. Lee, H.C., Shibata, H., Ogawa, S., Maki, K., Ikuta, K. J. Immunol. (2005) [Pubmed]
  19. Successful treatment of intracranial gliomas in rat by oligodeoxynucleotides containing CpG motifs. Carpentier, A.F., Xie, J., Mokhtari, K., Delattre, J.Y. Clin. Cancer Res. (2000) [Pubmed]
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