Identification of an Enhancer Required for the Expression of a Mouse Major Urinary Protein Gene in the Submaxillary Gland

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1991 Aug 1

PMID 2072918

Citations 3

Authors

H J Son

K Shahan

M Rodriguez

E Derman

F Costantini

Affiliations

Soon will be listed here.

Abstract

The MUP1.5b gene was previously found to be expressed specifically in the submaxillary gland and at high levels when introduced into mice as a transgene including 4.7 kb of 5'-flanking DNA and 0.3 kb of 3'-flanking DNA. To localize regulatory elements responsible for this tissue-specific pattern of expression, we tested the expression of three additional MUP1.5b transgenes including various amounts of 5'-flanking DNA. These experiments indicated that sequences between -1.85 and -3.46 kb from the transcription initiation site were required for high-level expression in the submaxillary gland. The presence of regulatory elements in this region was also suggested by the detection of a DNase I-hypersensitive site, seen only in submaxillary gland nuclei, at position -2.5 kb upstream from the MUP1.5a gene, a member of the same MUP gene subfamily and virtually identical to the MUP1.5b gene. Further evidence for enhancer activity was provided by the ability of the 1.6-kb DNA fragment including sequences between -1.85 and -3.46 kb to stimulate the expression of an otherwise inactive MUP1.5b-chloramphenicol acetyltransferase fusion gene specifically in the submaxillary gland. The nucleotide sequence of this 1.6-kb DNA fragment was found to be identical for the MUP1.5a and MUP1.5b genes. Together, these results provide the first localization of a cis-acting regulatory sequence involved in the differential tissue-specific expression of the MUP gene family.

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References

Finlayson J, Asofsky R, Potter M, Runner C . Major urinary protein complex of normal mice: origin. Science. 1965; 149(3687):981-2. DOI: 10.1126/science.149.3687.981. View

Banerji J, Olson L, Schaffner W . A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell. 1983; 33(3):729-40. DOI: 10.1016/0092-8674(83)90015-6. View

Hastie N, Held W, Toole J . Multiple genes coding for the androgen-regulated major urinary proteins of the mouse. Cell. 1979; 17(2):449-57. DOI: 10.1016/0092-8674(79)90171-5. View

Derman E . Isolation of a cDNA clone for mouse urinary proteins: age- and sex-related expression of mouse urinary protein genes is transcriptionally controlled. Proc Natl Acad Sci U S A. 1981; 78(9):5425-9. PMC: 348758. DOI: 10.1073/pnas.78.9.5425. View

Gorman C, Merlino G, Willingham M, Pastan I, Howard B . The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc Natl Acad Sci U S A. 1982; 79(22):6777-81. PMC: 347216. DOI: 10.1073/pnas.79.22.6777. View

SHAW P, Held W, Hastie N . The gene family for major urinary proteins: expression in several secretory tissues of the mouse. Cell. 1983; 32(3):755-61. DOI: 10.1016/0092-8674(83)90061-2. View

Gillies S, Morrison S, Oi V, Tonegawa S . A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell. 1983; 33(3):717-28. DOI: 10.1016/0092-8674(83)90014-4. View

Knopf J, Gallagher J, Held W . Differential, multihormonal regulation of the mouse major urinary protein gene family in the liver. Mol Cell Biol. 1983; 3(12):2232-40. PMC: 370094. DOI: 10.1128/mcb.3.12.2232-2240.1983. View

BELLARD M, Dretzen G, Bellard F, Oudet P, Chambon P . Disruption of the typical chromatin structure in a 2500 base-pair region at the 5' end of the actively transcribed ovalbumin gene. EMBO J. 1982; 1(2):223-30. PMC: 553024. DOI: 10.1002/j.1460-2075.1982.tb01151.x. View

10.

Clark A, Hickman J, Bishop J . A 45-kb DNA domain with two divergently orientated genes is the unit of organisation of the murine major urinary protein genes. EMBO J. 1984; 3(9):2055-64. PMC: 557643. DOI: 10.1002/j.1460-2075.1984.tb02091.x. View

11.

Nowock J, Borgmeyer U, Puschel A, Rupp R, Sippel A . The TGGCA protein binds to the MMTV-LTR, the adenovirus origin of replication, and the BK virus enhancer. Nucleic Acids Res. 1985; 13(6):2045-61. PMC: 341134. DOI: 10.1093/nar/13.6.2045. View

12.

Bishop J, Selman G, Hickman J, Black L, Saunders R, Clark A . The 45-kb unit of major urinary protein gene organization is a gigantic imperfect palindrome. Mol Cell Biol. 1985; 5(7):1591-600. PMC: 367277. DOI: 10.1128/mcb.5.7.1591-1600.1985. View

13.

Jones K, Yamamoto K, Tjian R . Two distinct transcription factors bind to the HSV thymidine kinase promoter in vitro. Cell. 1985; 42(2):559-72. DOI: 10.1016/0092-8674(85)90113-8. View

14.

Clark A, Ghazal P, Bingham R, Barrett D, Bishop J . Sequence structures of a mouse major urinary protein gene and pseudogene compared. EMBO J. 1985; 4(12):3159-65. PMC: 554636. DOI: 10.1002/j.1460-2075.1985.tb04059.x. View

15.

Clark A, Ma X, Bishop J . Analysis of mouse major urinary protein genes: variation between the exonic sequences of group 1 genes and a comparison with an active gene out with group 1 both suggest that gene conversion has occurred between MUP genes. EMBO J. 1985; 4(12):3167-71. PMC: 554637. DOI: 10.1002/j.1460-2075.1985.tb04060.x. View

16.

Treisman R . Identification of a protein-binding site that mediates transcriptional response of the c-fos gene to serum factors. Cell. 1986; 46(4):567-74. DOI: 10.1016/0092-8674(86)90882-2. View

17.

Briggs M, Kadonaga J, Bell S, Tjian R . Purification and biochemical characterization of the promoter-specific transcription factor, Sp1. Science. 1986; 234(4772):47-52. DOI: 10.1126/science.3529394. View

18.

Jones K, Kadonaga J, Rosenfeld P, Kelly T, Tjian R . A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication. Cell. 1987; 48(1):79-89. DOI: 10.1016/0092-8674(87)90358-8. View

19.

Angel P, Imagawa M, Chiu R, Stein B, Imbra R, Rahmsdorf H . Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987; 49(6):729-39. DOI: 10.1016/0092-8674(87)90611-8. View

20.

Shahan K, Gilmartin M, Derman E . Nucleotide sequences of liver, lachrymal, and submaxillary gland mouse major urinary protein mRNAs: mosaic structure and construction of panels of gene-specific synthetic oligonucleotide probes. Mol Cell Biol. 1987; 7(5):1938-46. PMC: 365299. DOI: 10.1128/mcb.7.5.1938-1946.1987. View