Genomic DNA sequence and organization of a TL-like gene in the grc-G/C region of the rat

Abstract

Genes in the grc-G/C region, which is linked to the rat major histocompatibility complex, influence the control of growth, development, and susceptibility to chemical carcinogens. As an initial approach to analyzing the structure and organization of these genes, a class I hybridizing fragment designated RT(5. 8) was isolated from an R21 genomic DNA library and sequenced from overlapping restriction enzyme fragments. The RT(5. 8) clone has 5788 base pairs and contains the eight exons characteristic of a class I gene. There are CAAT and TATA boxes upstream of the signal peptide, and the recognition sequence that precedes the site of polyadenylation is located downstream from the third cytoplasmic domain. Comparison of the RT(5. 8) gene with representative class I genes from the rat and other species shows that the nucleotide sequences of RT(5. 8) have a high level of similarity to those of TL region genes of several strains of mice. The peptide sequence deduced from the RT(5.8) clone is distinct from all previously published class I gene sequences, and at many positions there are amino acid residues that are unique to the RT(5.8) sequence. Probes have been isolated from the third exon and from the 5' and 3' flanking regions of the RT(5. 8) clone, and Southern blot analysis with genomic DNA of various rat strains shows that these probes are specific for the RT(5. 8) fragment. Northern blot analysis shows that the gene is transcribed in the thymus but not in the liver or spleen. The RT(5. 8) sequence is more similar to some mouse TL genes (especially in the a2 and cytoplasmic domains and in the 5' and 3' untranslated regions) than it is to other rat class I genes. Hence, TL-like genes are not restricted to the mouse.The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession number M74822.

Physical Map and Expression Profile of Genes of the Telomeric Class I Gene Region of the Rat MHC

“…Thus, whereas the localization of this subregion immediately telomeric to Bat1 corresponds to the H2-D/L/Q region of the mouse, the individual genes are not orthologous. The RT-BM1 (RT1-S3) gene in the second class I gene cluster is assumed to be orthologous to the mouse H2-T23 gene (27,28), which encodes the Qa-1 molecule, and the RT1-N1 gene is reported to be orthologous to H2-T10 and T22 (30). Furthermore, the Grc probe, defining the Grc region in the second cluster, has been shown to cross-hybridize to sequences flanking the (44).…”

“…3C). The D20Arb2 microsatellite (18,19), derived from the RT1-N1 gene (30), also maps to the second class I subregion at multiple positions (Fig. 2).…”

“…2), the RT-BM1 gene (26 -28), which is identical to RT1-S3 (29), could be assigned to fragment 4.4 on the basis of specific hybridization and partial sequence information obtained from the 3Ј-utr of fragment 4.4. Similarly, the RT1-N1 gene (30) was identified according to specific hybridization and partial sequence data and assigned to BamHI fragment 4.6.…”

Sequence analysis of the promoter regions of the classical class I gene RT1.A l and two other class I genes of the rat MHC

“…In the region corresponding to RT1.A 1 -393 to +64 a total of 13 H2K-characteristic substitutions and 15 H2D/L-specific substitutions are shared by the three rat sequences. Full genomic sequences including the promoter region have previously been reported for three other rat class I genes, RT1.N (RT5.8), RT1.Q (RT6.8), and RT1.A-4 (Kirisits et al 1992;Rushton et al 1993;Kryspin-Sorensen et al 1991). In accordance with the classification of RT1.N as Tla-like and RT1.…”

Activation Transcription Factor 1 Involvement in the Regulation of Murine H-2D Expression

“…One of these, RT 1.C, has been shown to be functional and does indeed contain the H-2 BF1 target sequence (32). Of the three remaining isolates, two are functional but are TLa-like (33,34), and the third is a pseudogene (35). Two swine genes were also identified and found to contain the binding sequence; one of these has been shown to be functional, while the other has not (36,37).…”