title: The CCAAT box binding factor, NF-Y, is required for thyroid hormone regulation of rat liver S14 gene transcription.
abstract: Triiodothyronine (T3) activates rat liver S14 gene transcription through T3 receptors (TRbeta) binding distal thyroid hormone response elements located between -2.8 and -2.5 kilobase pairs upstream from the transcription start site. Previous studies suggested that proximal promoter elements located between -220 to -80 base pairs upstream from the 5' end of the S14 gene were involved in hormone activation of the S14 gene. This report identifies an inverted CCAAT box (or Y box) at -104ATTGG-100 as a core cis-regulatory element. Gel shift studies using rat liver nuclear proteins show that at least three CCAAT-binding factors interact with this region as follows: NF-Y and c/EBP-related proteins formed major complexes, whereas NF-1/CTF forms a minor complex in gel shift assay. Mutation of the Y box indicated that loss of NF-Y binding, but not c/EBP or NF-1, correlated closely with a decline in basal activity and a loss of T3-mediated transactivation. Substitution of the S14 Y box in reporter genes with elements binding only NF-Y elevated basal activity and T3-mediated transactivation, whereas substitution with elements binding c/EBP-related proteins or SP1 displayed low basal activity and T3-mediated transactivation. These studies indicate that NF-Y and TRbeta functionally interact to confer T3 control to the S14 gene.
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, Michigan 48824, USA. Jump@pilot.msu.edu
authors.forename: D B
authors.initials: DB
authors.lastname: Jump
authors.forename: M V
authors.initials: MV
authors.lastname: Badin
authors.forename: A
authors.initials: A
authors.lastname: Thelen
mesh_terms: D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011506:Proteins / Q000235:genetics*; D051381:Rats; D017384:Sequence Deletion; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000502:physiology*; D014284:Triiodothyronine / Q000502:physiology*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011506:Proteins; C051065:THRSP protein, human; C501478:Thrsp protein, rat; D014157:Transcription Factors; D014284:Triiodothyronine