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

• Alterations included loss of methylation with biallelic expression of U2af1-rs1, maternal methylation and predominantly maternal expression of Igf2, and biallelic methylation and expression of Igf2r [15].
• The mouse U2af1-rs1 gene is an endogenous imprinted gene on the proximal region of chromosome 11 [16].
• To ask whether DNA methylation is associated with histone deacetylation, we produced mice with transgene-induced methylation at the paternal allele of U2af1-rs1 [17].
• We have proposed the neomorphic origin of the U2af1-rs1 gene by retrotransposition and the particular mechanism of genomic imprinting of ectopic genes [16].
• The U2af1-rs1 gene lies within a differentially methylated region (DMR), while Snrpn has a 5' DMR (DMR1) with sequences homologous to the imprinting control center of the Prader-Willi/Angelman region [17].

Anatomical context of Zrsr1

• Essentially the same patterns of differential acetylation were found in embryonic stem (ES) cells, embryo fibroblasts, and adult liver from F1 mice and in ES cells from mice that were dipaternal or dimaternal for U2af1-rs1 [17].
• We conclude that the imprints of the H19, U2af1-rs1, and Igf2 genes are maintained in lymphocytes in adult mice [18].
• Inhibition of histone deacetylases alters allelic chromatin conformation at the imprinted U2af1-rs1 locus in mouse embryonic stem cells [19].
• Here we report an artificial system in which expression and methylation of the endogenous imprinted gene U2af1-rs1 can be affected by interaction with its own transgene in the testis [20].
• Detailed methylation analyses of the U2af1-rs1 CGI in germ cells led to identification of a region with oocyte-specific methylation [21].

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].

References