Insulin represses transcription of the thyroid stimulating hormone beta-subunit gene through increased recruitment of nuclear factor I.
Although the regulation of thyroid stimulating hormone β-subunit gene (TSHβ) has been intensively studied, the functions of transcription factors involved are not fully understood. The authors found that the -615/-516 promoter region of the TSHβ interacts specifically with nuclear proteins derived from pituitary tissue or from cultured thyrotroph cells. The actual binding site at the nucleotide level, as revealed by DNase I protection assay, includes the consensus sequence for nuclear factor I (NFI). RT-PCR analysis indicated that NFI-B expression is restricted to thyrotroph cells in the anterior pituitary. EMSA and ChIP analysis showed that NFI-B binds most efficiently to the -588/-560 region of TSHβ promoter. The forced expressions of NFI-B markedly reduced TSHβ promoter activity and its mRNA expression. Furthermore, it was also shown that the -588/-560 region is involved in the insulin-mediated repression of the TSHβ. It was of particular interest to observe that NFI-B was recruited to the -588/-560 region of the TSHβ promoter in an insulin-dependent manner. Taken together, this study provides new insights of the delicate regulations of energy metabolism and hormonal homeostasis.
Kim
Kee Kwang
KK
Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 305-764, Republic of Korea.
Park
Key Sun
KS
Song
Seok Bean
SB
Kim
Kyoon Eon
KE
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000166:cytology; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D037322:Thyrotropin, beta Subunit / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D007328:Insulin; D051839:NFI Transcription Factors; D037322:Thyrotropin, beta Subunit; D014157:Transcription Factors