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Gene Review

Zrsr1  -  zinc finger (CCCH type), RNA binding motif...

Mus musculus

Synonyms: 35kDa, CCCH type zinc finger, RNA-binding motif and serine/arginine rich protein 1, D11Ncvs75, Irlgs2, SP2, ...
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Disease relevance of Zrsr1

  • An analysis of DNaseI hypersensitivity of a putative promoter of U2af1-rs1 showed an open chromatin conformation only on the unmethylated, expressed paternal allele [1].
  • The cells were fused with the plasmacytoma line SP2/0Ag14 [2].
  • The transfer of these expression vectors containing mouse-human chimeric immunoglobulin genes into Sp2/0 mouse myeloma cells resulted in the production of functional IgG that retained the specific binding to the surface antigen 17-1A expressed on colorectal carcinoma cells [3].
  • Ascites production of Sp2/0 transfectants is sufficiently high (900 micrograms/ml) for initial in vivo studies with humanized T84.66 [4].
  • Syngeneic monoclonal antibodies (MoAb) to Moloney sarcoma cells (MSC) were produced by fusion of spleen cells from MSC regressor mice to myeloma SP2/0 [5].

Psychiatry related information on Zrsr1

  • To investigate the nature of these Id' molecules, spleens from such anti-idiotype-treated mice were fused with the SP2/0 myeloma to produce monoclonal Id' antibodies [6].

High impact information on Zrsr1

  • Molecular analysis of the genomic region of one of the loci (Irigs2) resulted in the discovery of the paternally imprinted U2afbp-rs gene within a previously identified imprinted region on mouse chromosome 11 (refs 5, 7) [7].
  • In this in vivo study, histone methylation and acetylation are investigated along the imprinted mouse genes Snrpn, Igf2r and U2af1-rs1 [8].
  • Spleen cells were subsequently fused with Sp2/0 mouse myeloma cells, the resulting hybridomas were cloned, and their secreted Ig was screened for reactivity with antigens belonging to the Golgi complex [9].
  • In Sp2 cells, cAMP analogs, forskolin, and isobutylmethylxanthine inhibited cell proliferation and enhanced LPA action in an additive manner, suggesting that an LPA-elicited increase in cAMP-mediated signaling was responsible for the antimitogenic response [10].
  • In NIH 3T3 and Sp2 cells, LPA elicited an increase in inositol trisphosphate and a subsequent transient increase in free cytoplasmic Ca2+ [10].

Chemical compound and disease context of Zrsr1

  • To accomplish this, a monoclonal antibody against the group C capsular polysaccharide was developed by the fusion of splenocytes from mice immunized with Neisseria meningitidis group C strain MP13 with Sp2/0-Ag14 plasmacytoma cells [11].
  • Monoclonal antibodies against the Shigella flexneri lipopolysaccharide (LPS) were generated in two fusions by using the myeloma cell line Sp2/0 as a fusion partner with spleen cells from BALB/c mice immunized with S. flexneri serotypes 1b and 3a bacteria [12].
  • Mouse hybrid cell clones secreting antigonadotropin releasing hormone monoclonal antibody were developed by fusion of SP2/O-Ag 1.4 myeloma cells with splenocytes of mouse immunized with gonadotropin releasing hormone (GnRH) tagged to tetanus toxoid [13].
  • The authors developed the first rabbit anti-PgR mAb (clone SP2) used in IHC on formalin-fixed, paraffin-embedded tissue sections from breast carcinomas [14].

Biological context of Zrsr1


Anatomical context of Zrsr1


Associations of Zrsr1 with chemical compounds

  • For H4, underacetylation of the maternal allele was exclusively (U2af1-rs1) or predominantly (Snrpn) at lysine 5 [17].
  • TSA treatment of ES cells did not affect DNA methylation or expression of U2af1-rs1, but was sufficient to increase DNase I sensitivity along the maternal allele to a level comparable with that of the paternal allele [19].
  • The present work analyzes the involvement of these mechanisms in the expression of the U2af1-rs1 imprinted gene during the differentiation process of embryonic stem (ES) cells induced by retinoic acid [22].
  • Myelomas are antibody-secreting tumor cells derived from terminally differentiated B lymphocytes, and previous work from our laboratory showed that murine SP2/0 myeloma cells and derived B-cell hybridomas were highly sensitive to apoptosis induction by a block of gene expression (cycloheximide) [23].
  • The hybridoma clone was obtained by fusing Sp2/0- Ag14 myeloma cells with splenocytes from Balb/C mice which had been immunized with n-octyl glucoside solubilized proteins from isolated PC12 cell plasma membranes [24].

Other interactions of Zrsr1

  • Restriction mapping analysis using YAC and pulse-field gel electrophoresis showed that Cct4 is located within a region about 300 kb from the imprinted gene U2af1-rs1 [25].
  • Allele-specific methylation is limited to a region around U2af1-rs1 in an intron of Murr1 [16].
  • Meg1/Grb10 maps about 15 cM from U2af1-rs1 and is separated by conserved regions showing homology with two different human chromosomes [26].
  • These results suggest that allele-specific hypermethylation covering the gene and its upstream CpG island plays a role in maternal allele repression of U2af1-rs1, which is reflected in altered chromatin conformation of DNaseI hypersensitive sites [1].
  • We have cloned and analyzed the mouse U2af1-rs2 gene based on its sequence similarity to the imprinted gene U2af1-rs1 (SP2) [27].

Analytical, diagnostic and therapeutic context of Zrsr1

  • The relationship between DNA methylation and histone acetylation at the imprinted mouse genes U2af1-rs1 and Snrpn is explored by chromatin immunoprecipitation (ChIP) and resolution of parental alleles using single-strand conformational polymorphisms [17].
  • However, northern blot and real-time reverse transcription-polymerase chain reaction analysis showed a higher expression of the U2af1-rs1 gene in differentiated ES cells and in embryoid bodies than in undifferentiated ones [22].
  • By DNA digestion with methylation-dependent or independent restriction enzymes and consecutive Southern blot, we have found that methylation of the U2af1-rs1 gene increases in differentiated ES cells and in embryoid bodies [22].
  • To determine whether the U2afbp-rs gene is regulated by imprinting in the early embryo and to examine its normal temporal pattern of expression, we used a new quantitative RT-PCR approach to compare U2afbp-rs gene expression between androgenetic and gynogenetic embryos and to monitor U2afbp-rs expression during normal preimplantation embryogenesis [28].
  • Spleen cells of this rat were then fused with mouse Sp2/0-Ag14 myeloma cells and the antibodies produced by the hybrid cells were detected by double immunoprecipitation using the 125I-labeled receptor [29].


  1. 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]
  2. Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: A new reagent for detection of DNA replication. Gratzner, H.G. Science (1982) [Pubmed]
  3. Chimeric antibody with human constant regions and mouse variable regions directed against carcinoma-associated antigen 17-1A. Sun, L.K., Curtis, P., Rakowicz-Szulczynska, E., Ghrayeb, J., Chang, N., Morrison, S.L., Koprowski, H. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  4. Cloning of the genes for T84.66, an antibody that has a high specificity and affinity for carcinoembryonic antigen, and expression of chimeric human/mouse T84.66 genes in myeloma and Chinese hamster ovary cells. Neumaier, M., Shively, L., Chen, F.S., Gaida, F.J., Ilgen, C., Paxton, R.J., Shively, J.E., Riggs, A.D. Cancer Res. (1990) [Pubmed]
  5. Therapy of a murine sarcoma using syngeneic monoclonal antibody. Kennel, S.J., Lankford, T., Flynn, K.M. Cancer Res. (1983) [Pubmed]
  6. Anti-idiotypes against anti-H-2 monoclonal antibodies: structural analysis of the molecules induced by in vivo anti-idiotype treatment. Bluestone, J.A., Krutzsch, H.C., Auchincloss, H., Cazenave, P.A., Kindt, T.J., Sachs, D.H. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  7. Identification of Grf1 on mouse chromosome 9 as an imprinted gene by RLGS-M. Plass, C., Shibata, H., Kalcheva, I., Mullins, L., Kotelevtseva, N., Mullins, J., Kato, R., Sasaki, H., Hirotsune, S., Okazaki, Y., Held, W.A., Hayashizaki, Y., Chapman, V.M. Nat. Genet. (1996) [Pubmed]
  8. Allele-specific histone lysine methylation marks regulatory regions at imprinted mouse genes. Fournier, C., Goto, Y., Ballestar, E., Delaval, K., Hever, A.M., Esteller, M., Feil, R. EMBO J. (2002) [Pubmed]
  9. Characterization of cytoplasmically oriented Golgi proteins with a monoclonal antibody. Chicheportiche, Y., Vassalli, P., Tartakoff, A.M. J. Cell Biol. (1984) [Pubmed]
  10. Lysophosphatidic acid possesses dual action in cell proliferation. Tigyi, G., Dyer, D.L., Miledi, R. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  11. Development and characterization of an anti-idiotype antibody to the capsular polysaccharide of Neisseria meningitidis serogroup C. Westerink, M.A., Campagnari, A.A., Wirth, M.A., Apicella, M.A. Infect. Immun. (1988) [Pubmed]
  12. Monoclonal antibodies specific for Shigella flexneri lipopolysaccharides: clones binding to type I and type III:6,7,8 antigens, group 6 antigen, and a core epitope. Carlin, N.I., Lindberg, A.A. Infect. Immun. (1986) [Pubmed]
  13. Characteristics and bioefficacy of monoclonal antigonadotropin releasing hormone antibody. Gupta, S.K., Singh, O., Talwar, G.P. American journal of reproductive immunology and microbiology : AJRIM. (1985) [Pubmed]
  14. Development of new rabbit monoclonal antibody to progesterone receptor (Clone SP2): no heat pretreatment but effective for paraffin section immunohistochemistry. Huang, Z., Zhu, W., Meng, Y., Xia, H. Appl. Immunohistochem. Mol. Morphol. (2006) [Pubmed]
  15. Altered imprinted gene methylation and expression in completely ES cell-derived mouse fetuses: association with aberrant phenotypes. Dean, W., Bowden, L., Aitchison, A., Klose, J., Moore, T., Meneses, J.J., Reik, W., Feil, R. Development (1998) [Pubmed]
  16. Mouse U2af1-rs1 is a neomorphic imprinted gene. Nabetani, A., Hatada, I., Morisaki, H., Oshimura, M., Mukai, T. Mol. Cell. Biol. (1997) [Pubmed]
  17. DNA methylation is linked to deacetylation of histone H3, but not H4, on the imprinted genes Snrpn and U2af1-rs1. Gregory, R.I., Randall, T.E., Johnson, C.A., Khosla, S., Hatada, I., O'Neill, L.P., Turner, B.M., Feil, R. Mol. Cell. Biol. (2001) [Pubmed]
  18. Monoallelic expression of reactivated imprinted genes in embryonal carcinoma cell hybrids. Forejt, J., Saam, J.R., Gregorová, S., Tilghman, S.M. Exp. Cell Res. (1999) [Pubmed]
  19. Inhibition of histone deacetylases alters allelic chromatin conformation at the imprinted U2af1-rs1 locus in mouse embryonic stem cells. Gregory, R.I., O'Neill, L.P., Randall, T.E., Fournier, C., Khosla, S., Turner, B.M., Feil, R. J. Biol. Chem. (2002) [Pubmed]
  20. Aberrant methylation of an imprinted gene U2af1-rs1(SP2) caused by its own transgene. Hatada, I., Nabetani, A., Arai, Y., Ohishi, S., Suzuki, M., Miyabara, S., Nishimune, Y., Mukai, T. J. Biol. Chem. (1997) [Pubmed]
  21. Comparative analyses of genomic imprinting and CpG island-methylation in mouse Murr1 and human MURR1 loci revealed a putative imprinting control region in mice. Zhang, Z., Joh, K., Yatsuki, H., Wang, Y., Arai, Y., Soejima, H., Higashimoto, K., Iwasaka, T., Mukai, T. Gene (2006) [Pubmed]
  22. Epigenetic regulation of the imprinted U2af1-rs1 gene during retinoic acid-induced differentiation of embryonic stem cells. Andollo, N., Boyano, M.D., Andrade, R., Aréchaga, J.M. Dev. Growth Differ. (2006) [Pubmed]
  23. Role of bcl-X(L) in the control of apoptosis in murine myeloma cells. Gauthier, E.R., Piché, L., Lemieux, G., Lemieux, R. Cancer Res. (1996) [Pubmed]
  24. A monoclonal antibody modulates the interaction of nerve growth factor with PC12 cells. Chandler, C.E., Parsons, L.M., Hosang, M., Shooter, E.M. J. Biol. Chem. (1984) [Pubmed]
  25. Chromosomal assignment and imprinting tests for the mouse delta subunit of the cytosolic chaperonin containing TCP-1 (Cct4) gene to proximal chromosome 11. Nabetani, A., Hatada, I., Morisaki, H., Mukai, T. Genomics (1996) [Pubmed]
  26. Association of a redefined proximal mouse chromosome 11 imprinting region and U2afbp-rs/U2af1-rs1 expression. Cattanach, B.M., Shibata, H., Hayashizaki, Y., Townsend, K.M., Ball, S., Beechey, C.V. Cytogenet. Cell Genet. (1998) [Pubmed]
  27. Cloning and mapping of the U2af1-rs2 gene with a high transmission distortion in interspecific backcross progeny. Yamaoka, T., Hatada, I., Kitagawa, K., Wang, X., Mukai, T. Genomics (1995) [Pubmed]
  28. Stage-specific induction and regulation by genomic imprinting of the mouse U2afbp-rs gene during preimplantation development. Latham, K.E., Rambhatla, L., Hayashizaki, Y., Chapman, V.M. Dev. Biol. (1995) [Pubmed]
  29. Monoclonal antibody to chicken oviduct progesterone receptor. Radanyi, C., Joab, I., Renoir, J.M., Richard-Foy, H., Baulieu, E.E. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
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