Title | The CCAAT box binding factor, NF-Y, is required for thyroid hormone regulation of rat liver S14 gene transcription. |
Publication Type | Journal Article |
Year of Publication | 1997 |
Authors | Jump, DB, Badin, MV, Thelen, A |
Journal | J Biol Chem |
Volume | 272 |
Issue | 44 |
Pagination | 27778-86 |
Date Published | 1997 Oct 31 |
ISSN | 0021-9258 |
Keywords | Animals, CCAAT-Enhancer-Binding Proteins, Cells, Cultured, DNA-Binding Proteins, Enhancer Elements, Genetic, Gene Expression Regulation, Liver, Mutagenesis, Nuclear Proteins, Promoter Regions, Genetic, Protein Binding, Proteins, Rats, Sequence Deletion, Transcription Factors, Transcription, Genetic, Triiodothyronine |
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. |
DOI | 10.1074/jbc.272.44.27778 |
Alternate Journal | J. Biol. Chem. |
PubMed ID | 9346922 |
Grant List | R01 DK043220 / DK / NIDDK NIH HHS / United States DK43220 / DK / NIDDK NIH HHS / United States |