title: TTF-2 stimulates expression of 17 genes, including one novel thyroid-specific gene which might be involved in thyroid development.
abstract: Thyroid dysgenesis is the most frequent cause of congenital hypothyroidism, but its molecular pathophysiology is largely unknown. Our hypothesis that some genes downstream to thyroid transcription factor-2 (TTF-2) might be responsible for development of the thyroid prompted us to identify genes whose expression is stimulated by TTF-2. PCR products of cDNA clones obtained by a subtraction PCR method in TTF-2 expressing cell lines were screened with labeled cDNA by microarray analysis. We isolated 17 genes up-regulated by TTF-2, which were subsequently confirmed by quantitative reverse transcription-polymerase chain reaction (RT-PCR). One of them is a novel gene designated T1560 that showed a highly thyroid-specific expression pattern. Luciferase reporter assays showed that expression of all of the 14 genes tested was stimulated by both TTF-2 and TTF-1, another thyroid-specific transcription factor. Our results have important implications for understanding normal thyroid development as well as the molecular defects underlying thyroid dysgenesis.
authors.affiliation: Department of Clinical Laboratory Medicine, Dokkyo University School of Medicine, Kitakobayashi 880, Mibu, Tochigi 321-0293, Japan. a-hishi@dokkyomed.ac.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Hishinuma
authors.forename: Narumi
authors.initials: N
authors.lastname: Ohmika
authors.forename: Takashi
authors.initials: T
authors.lastname: Namatame
authors.forename: Tamio
authors.initials: T
authors.lastname: Ieiri
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D020869:Gene Expression Profiling; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D062085:RNA, Long Noncoding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013961:Thyroid Gland / Q000254:growth & development* / Q000378:metabolism*; D014018:Tissue Distribution / Q000235:genetics; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors; D008565:Membrane Proteins; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; C495180:T1560 protein, human