title: A 30-base-pair element in the first intron of SOX9 acts as an enhancer in ATDC5.
abstract: SOX9 is a transcription factor that is essential for chondrogenesis and testis differentiation, and haploinsufficiency of SOX9 causes campomelic dysplasia, severe skeletal malformation syndrome with variably penetrant XY sex reversal. Here we demonstrate that in several cell lines that express SOX9, 30-bp element in the first intron of human SOX9 gene act as a potential enhancer in the ATDC5 chondroprogenitor cell line, despite the apparent absence of cell-specific regulatory elements within a 5.5-kb promoter region. Deletion and site-specific mutational analyses reveal that the last 12 bp of the 30-bp element are critical for transcriptional activity, while 5'-half sequences are necessary for full transactivation. Gel retardation assays indicate the possible involvement of several binding factors along the length of this element. These results suggest that functionally interdependent elements in the 30-bp enhancer region of the first intron account for basal expression levels of Sox9 in ATDC5.
authors.affiliation: Department of Nature Medicine, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Morishita
authors.forename: T
authors.initials: T
authors.lastname: Kishino
authors.forename: K
authors.initials: K
authors.lastname: Furukawa
authors.forename: A
authors.initials: A
authors.lastname: Yonekura
authors.forename: Y
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: T
authors.initials: T
authors.lastname: Kanematsu
authors.forename: S
authors.initials: S
authors.lastname: Yamashita
authors.forename: T
authors.initials: T
authors.lastname: Tsukazaki
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D004252:DNA Mutational Analysis; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D006609:High Mobility Group Proteins / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D055758:SOX9 Transcription Factor; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D006609:High Mobility Group Proteins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C527933:Sox9 protein, mouse; D014157:Transcription Factors; D004247:DNA