A zinc finger homeodomain transcription factor binds specific thyroid hormone response elements.
Thyroid hormone receptors can act through response elements (TREs) having a wide variation of sequence. We screened for transcription factors that bind the rat (r) glycoprotein hormone alpha-subunit TRE (alpha-sub), and isolated a cDNA, termed zinc finger homeodomain enhancer-binding protein (Zfhep), which encodes two separate zinc finger domains (ZD1 and ZD2), and a region similar to homeodomains. DNA-binding assays show that ZD1 or ZD2 can bind the alpha-subunit, rat growth hormone, or thyrotropin beta (TSHbeta) gene TREs, but do not bind DR4 or palindromic (pal) TREs. Methylation interference footprinting demonstrates that Zfhep binds the alpha-sub overlapping the TR-binding site. Similarly, the ZD1 protein footprints over TR-binding halfsites of the rat growth hormone (rGH) and TSHbeta TREs. Hence, Zfhep binding is dependent on sequences within and outside the AGGTCA TR-binding halfsite. Interactions of non-receptor transcription factors (such as Zfhep) with certain TREs are important to modify gene-specific regulation by thyroid hormones.
Department of Biological and Biophysical Sciences, University of Louisville, School of Dentistry, Kentucky 40292, USA. dsdar101@homer.louisville.edu
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Darling
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Gaur
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Zhu
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism*; D018983:DNA Footprinting; D005786:Gene Expression Regulation; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013972:Thyrotropin / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000071799:Zinc Finger E-box-Binding Homeobox 1; D016335:Zinc Fingers
D015292:Glycoprotein Hormones, alpha Subunit; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C000630720:ZEB1 protein, rat; D000071799:Zinc Finger E-box-Binding Homeobox 1; D013972:Thyrotropin; D004247:DNA