title: Genomic organization and promoter analysis of mouse follistatin-related gene (FLRG).
abstract: Follistatin (FS) is well characterized as an activin-binding protein. Recently, a novel follistatin-like protein called follistatin-related gene (FLRG) that has a similar domain organization to that of follistatin has been identified. Like follistatins, FLRG binds activins and bone morphogenetic proteins (BMPs). To study the regulation of FLRG expression, we have analyzed the genomic organization and promoter of the mouse FLRG gene. The mouse FLRG gene consists of five exons, and each encodes discrete functional regions. The overall genomic structure of FLRG is similar to that of FS except that the FLRG gene is missing one exon that codes a third FS domain found in FS. The promoter that covers 2.5 kbp and is linked to a luciferase reporter construct is active in human cervical carcinoma HeLa cells as well as in human embryonic kidney (HEK293) cells. Deletion analysis of the promoter regions indicates that a proximal 550 base pairs are enough for basal FLRG promoter activity in the cell lines. FLRG promoter activity is significantly augmented by phorbol 12-myristate 13-acetate (PMA) treatment, but not by cAMP stimulation. By contrast, FS promoter is activatable either by cAMP or PMA. Thus, although FS and FLRG are structurally and functionally related, their modes of regulation by external stimuli are different.
authors.affiliation: Institute for Enzyme Research, The University of Tokushima, 3-18-15 Kuramoto, 770-8503, Tokushima, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Nakatani
authors.forename: Norio
authors.initials: N
authors.lastname: Yamakawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuzaki
authors.forename: Shunichi
authors.initials: S
authors.lastname: Shimasaki
authors.forename: Hiromu
authors.initials: H
authors.lastname: Sugino
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Tsuchida
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D005091:Exons / Q000235:genetics; D038681:Follistatin / Q000378:metabolism; D038702:Follistatin-Related Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D005796:Genes; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D038681:Follistatin; D038702:Follistatin-Related Proteins; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate