TTF-2 stimulates expression of 17 genes, including one novel thyroid-specific gene which might be involved in thyroid development.
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.
Hishinuma
Akira
A
Department of Clinical Laboratory Medicine, Dokkyo University School of Medicine, Kitakobayashi 880, Mibu, Tochigi 321-0293, Japan. a-hishi@dokkyomed.ac.jp
Ohmika
Narumi
N
Namatame
Takashi
T
Ieiri
Tamio
T
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
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