Molecular genetics of androgen-dependent and -independent expression of mouse sex-limited protein.

Stavenhagen, Jeffrey B.; Loreni, Fabrizio; Hemenway, C; Kalff, Martha; Robins, Diane M.

doi:10.1128/mcb.7.5.1716

Cited by 27 publications

(27 citation statements)

References 22 publications

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“…One of four B10.WR Slp genes, however, is more similar to the single androgendependent allele from B10.D2 mice; furthermore, an upstream region present in both of these Slp genes directed androgen-responsive transcription after transfection (35). In liver chromatin, hormone-responsive DNase-hypersensitive sites are located in the same upstream region, 2 kb from the Slp transcription start site (15), confirming its significance to expression in vivo.…”

mentioning

confidence: 62%

“…While it may affect the Slp promoter, it does not appear to affect transcription from the upstream region (for instance, pG2.9RA5 lacked this domain but was not more active than pG2.9R). This and other elements may have some cell specificity, like the lysozyme gene negative element (36), since flanking DNA (in pG2.6 and pG2.9) allowed CAT expression in L cells (35) and HepG2 cells (23) but not in T47D cells. In G221 stable transformants, expression of pG2.9 was detectable, but it did not respond to hormone.…”

Section: Hormonal Regulation Of Mouse Sex-limited Proteinmentioning

confidence: 99%

“…Ltkcells were maintained as described (38). G221 cells were transfected by the CaPO4 method (38) as detailed previously (35), and T47D cells were transfected by the DEAE-dextran method (4 (27). DNase I footprint analysis.…”

Section: Hormonal Regulation Of Mouse Sex-limited Proteinmentioning

confidence: 99%

“…androgen-independent Slp expression, such as B10.WR, multiple Slp genes exist in the genome; apparent recombination with C4 in 5' regions is likely to account for their C4-like regulation (22,29,35). One of four B10.WR Slp genes, however, is more similar to the single androgendependent allele from B10.D2 mice; furthermore, an upstream region present in both of these Slp genes directed androgen-responsive transcription after transfection (35).…”

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confidence: 99%

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A complex androgen-responsive enhancer resides 2 kilobases upstream of the mouse Slp gene.

Loreni¹,

Stavenhagen²,

Kalff³

et al. 1988

Mol. Cell. Biol.

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confidence: 62%

Section: Hormonal Regulation Of Mouse Sex-limited Proteinmentioning

confidence: 99%

Section: Hormonal Regulation Of Mouse Sex-limited Proteinmentioning

confidence: 99%

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confidence: 99%

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A complex androgen-responsive enhancer resides 2 kilobases upstream of the mouse Slp gene.

Loreni¹,

Stavenhagen²,

Kalff³

et al. 1988

Mol. Cell. Biol.

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“…Information to date suggests that genetic elements within or near the structural gene play an important role (8,10,20,22,24,27). Several studies have indicated that androgen regulation of mouse mammary tumor virus expression is conferred by a sequence, termed the hormone response element, that is also responsible for progesterone and glucocorticoid regulation of virus transcription (10,24); this element is located upstream of the transcription initiation site and may be a binding site for the androgen receptor.…”

Section: Discussionmentioning

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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Retrotransposons and the evolution of mammalian gene expression

Robins

Samuelson

1993

Transposable Elements and Evolution

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Transposable elements, and retroviral-like elements in particular, are a rich potential source of genetic variation within a host's genome. Many mutations of endogenous genes in phylogenetically diverse organisms are due to insertion of elements that affect gene expression by altering the normal pattern of regulation. While few such associations are known to have been maintained over time, two recently elucidated examples suggest transposable elements may have a significant impact in evolution of gene expression. The first example, concerning the mouse sex-limited protein (Slp), clearly establishes that ancient retroviral enhancer sequences now confer hormonal dependence on the adjacent gene. The second example shows that within the human amylase gene family, salivary specific expression has arisen due to inserted sequences, deriving perhaps from a conjunction of two retrotransposable elements.

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Molecular genetics of androgen-dependent and -independent expression of mouse sex-limited protein.

Cited by 27 publications

References 22 publications

A complex androgen-responsive enhancer resides 2 kilobases upstream of the mouse Slp gene.

A complex androgen-responsive enhancer resides 2 kilobases upstream of the mouse Slp gene.

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

Retrotransposons and the evolution of mammalian gene expression

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