title: Identification of an enhancer required for the expression of a mouse major urinary protein gene in the submaxillary gland.
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.
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
authors.forename: H J
authors.initials: HJ
authors.lastname: Son
authors.forename: K
authors.initials: K
authors.lastname: Shahan
authors.forename: M
authors.initials: M
authors.lastname: Rodriguez
authors.forename: E
authors.initials: E
authors.lastname: Derman
authors.forename: F
authors.initials: F
authors.lastname: Costantini
mesh_terms: D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000502:physiology; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011506:Proteins / Q000235:genetics* / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D015183:Restriction Mapping; D013363:Submandibular Gland / Q000502:physiology*
chemical_list: D011506:Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C035737:major urinary proteins; D015500:Chloramphenicol O-Acetyltransferase