Polymorphism in an androgen-regulated mouse gene is the result of the insertion of a B1 repetitive element into the transcription unit.

King, Donna; Snider, Lauren; Lingrel, Jerry B.

doi:10.1128/mcb.6.1.209

Cited by 29 publications

(10 citation statements)

References 36 publications

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“…79 % similarity to the Bl consensus sequence [38]. At the 3' end of the repeat there is a G/T-rich region (cDNA sequence 2619-2635), typical of other Bl repeats [39].…”

Section: Isolation and Characterization Of The Mouse MCM Genementioning

confidence: 97%

Genomic structure of murine methylmalonyl-CoA mutase: evidence for genetic and epigenetic mechanisms determining enzyme activity

Wilkemeyer

Andrews

Ledley

1993

Biochemical Journal

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Methylmalonyl-CoA mutase (MCM) is a nuclear-encoded mitochondrial matrix enzyme. We have reported characterization of murine MCM and cloning of a murine MCM cDNA and now describe the murine Mut locus, its promoter and evidence for tissue-specific variation in MCM mRNA, enzyme and holo-enzyme levels. The Mut locus spans 30 kb and contains 13 exons constituting a unique transcription unit. A B1 repeat element was found in the 3′ untranslated region (exon 13). The transcription initiation site was identified and upstream sequences were shown to direct expression of a reporter gene in cultured cells. The promoter contains sequence motifs characteristic of: (1) TATA-less housekeeping promoters; (2) enhancer elements purportedly involved in co-ordinating expression of nuclear-encoded mitochondrial proteins; and (3) regulatory elements including CCAAT boxes, cyclic AMP-response elements and potential AP-2-binding sites. Northern blots demonstrate a greater than 10-fold variation in steady-state mRNA levels, which correlate with tissue levels of enzyme activity. However, the ratio of holoenzyme to total enzyme varies among different tissues, and there is no correlation between steady-state mRNA levels and holoenzyme activity. These results suggest that, although there may be regulation of MCM activity at the level of mRNA, the significance of genetic regulation is unclear owning to the presence of epigenetic regulation of holoenzyme formation.

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“…79 % similarity to the Bl consensus sequence [38]. At the 3' end of the repeat there is a G/T-rich region (cDNA sequence 2619-2635), typical of other Bl repeats [39].…”

Section: Isolation and Characterization Of The Mouse MCM Genementioning

confidence: 97%

Genomic structure of murine methylmalonyl-CoA mutase: evidence for genetic and epigenetic mechanisms determining enzyme activity

Wilkemeyer

Andrews

Ledley

1993

Biochemical Journal

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“…All of these different mRNAs are produced by the transcription of a single gene (2,10). Previous work has reported two different polyadenylation sites that are recognized to produce the 1450 and 1950 nt mRNAs In the kidney (9). In this paper we identify a third polyadenylation site, responsible for the generation of the 1350 nt species.…”

Section: Introductionmentioning

confidence: 66%

“…Three RP2 species that are most abundant in kidney, liver, and submaxillary gland are 1350, 1450, and 1950 nt in length (2,9). These same three mRNAs are expressed at low levels in brain and muscle, but the more abundant RP2 mRNAs in these tissues are 1050, 1150, and 1650 nt long (2, D.K., unpublished observations).…”

Section: Introductionmentioning

confidence: 99%

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Amino acid sequence of the testosterone-regulated mouse kidney RP2 protein deduced from its complementary DNA sequence

1986

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The major forms of testosterone-regulated RP2 messenger RNA (also known as MAK mRNA and pMK908) in the mouse kidney were characterized by examining eDNA and genomic clones. Three sizes of RP2 mRNA are detected by Northern blot analysis and these were shown to result from polyadenylation at three distinct sites within the primary transcript of this single-copy gene. The complete RP2 mRNA sequence was obtained from overlapping cDNA clones, revealing an open reading frame of 357 amino acids that corresponds to a protein of 40,365 daltons. The detection of RP2 mRNA in all tissues examined to date suggests that the RP2 protein may function in a housekeeping role in all cells. This is supported by the finding of a high percentage of G + C residues at the 5' end of the gene, including a sequence homologous to the binding site of the transcription factor Spl, which has been suggested to affect the regulation of other housekeeping genes that have been characterized. An examination of the amino acid sequence indicates that the RP2 protein is proline-rich and is composed of alternating alpha-helix and beta-sheet regions. RP2 is probably not integrated into a membrane structure in the cell as it does not appear to contain hydrophobic regions capable of spanning a membrane.

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“…RP2 encodes at least two mRNAs that undergo about a 10-to 12-fold induction in the kidneys of female mice treated with testosterone (3,26). These mRNAs, which differ in the lengths of their 3' untranslated regions (18), encode a polypeptide of 357 amino acids in length as deduced from cDNA sequencing (19). The function of the RP2-encoded protein is not known.…”

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confidence: 99%

Molecular genetics of androgen-inducible RP2 gene transcription in the mouse kidney.

Rheaume¹,

Barbour²,

Tseng-Crank³

et al. 1989

Mol. Cell. Biol.

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Androgen control of the RP2 gene in the mouse kidney has been modified during evolution. In inbred mice (Mus domesticus), the concentrations of mRNAs encoded by RP2 undergo a 10-to 12-fold induction in response to testosterone; in other Mus species (e.g., Mus hortulanus and Mus carol), induction ranges from none to about two-to fourfold. In this communication, we show that androgens induced RP2 transcription in M. domesticus, although this induction may not have fully accounted for the increase in mRNA levels. Reduced mRNA inducibility in M. hortulanus and in several other species was associated with an absence of transcriptional induction. Analysis of an interspecies backcross population indicated that the difference in RP2 inducibility between M. domesticus and M. hortulanus was due to a single Mendelian locus tightly linked (0 of 47 recombinants) to RP2. The RP2 gene was found to contain at least two promoters, only one of which was highly sensitive to testosterone. These results indicate that induction of the RP2 mRNAs, as well as interspecies variations in RP2 inducibility, are primarily a consequence of effects on this promoter.The evolutionary process results in the generation of interspecies variations in gene expression (12,13,23,33). These variations derive, presumably, from mutations in regulatory elements. The study of naturally occurring alterations in gene expression not only allows identification of these elements but also generates insights into the changes that the elements undergo during evolution. The mouse (genus Mus) has become useful for studies of mammalian gene regulation and evolution. A large number of wellcharacterized species (5-7) provides a pool of variability that has accumulated over a 10-million-year period. Indeed, considerable variation in gene activity has been identified among these species (2,11,16,25,29).Gene expression in the mouse kidney is regulated by androgens. In proximal tubule cells, testosterone induces the concentrations of a number of gene products; these inductions occur primarily at the mRNA level (see references 9 and 30 for recent reviews; F. G. Berger and G. Watson, Annu. Rev. Physiol., in press). The RP2 gene, which is linked to Gpi-J on mouse chromosome 7 (14), has become a useful model for androgen-modulated gene expression. RP2 encodes at least two mRNAs that undergo about a 10-to 12-fold induction in the kidneys of female mice treated with testosterone (3, 26). These mRNAs, which differ in the lengths of their 3' untranslated regions (18), encode a polypeptide of 357 amino acids in length as deduced from cDNA sequencing (19). The function of the RP2-encoded protein is not known.Nuclear run-on assays have indicated that induction of RP2 mRNAs, like the induction of several other androgenregulated mRNAs, is predominantly a posttranscriptional phenomenon, occurring at the level of transcript processing or stability (4). Recently, however, an in vivo assay has been used to show that androgens increase RP2 mRNA synthesis by about 3-to 4-fold (32), which sugg...

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Polymorphism in an androgen-regulated mouse gene is the result of the insertion of a B1 repetitive element into the transcription unit.

Cited by 29 publications

References 36 publications

Genomic structure of murine methylmalonyl-CoA mutase: evidence for genetic and epigenetic mechanisms determining enzyme activity

Genomic structure of murine methylmalonyl-CoA mutase: evidence for genetic and epigenetic mechanisms determining enzyme activity

Amino acid sequence of the testosterone-regulated mouse kidney RP2 protein deduced from its complementary DNA sequence

Molecular genetics of androgen-inducible RP2 gene transcription in the mouse kidney.

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