AP-1 and T3RE cis elements operate as a functional unit in the transcriptional control of the human malic enzyme gene.
The human malic enzyme (hME) promoter contains an inverted palindromic (IP4) 3,5,3'-triiodo-thyronine (T3) response element (T3RE) 15bp downstream from an activating protein-1 (AP-1) site. The purpose of this study was to analyze the functional relationship between both cis-acting elements. The following observations indicate that these two elements operate as a functional unit in controlling the human ME gene:T3 failed to stimulate transcription above the basal levels in cells overexpressing either TRb or TRb/retinoid acid receptor (RXR), indicating that TRbeta acts primarily as a transcriptional repressor in the context of the hME. Moreover, the finding of a repressive effect of TRbeta without DNA binding suggests the existence of both DNA-dependent and independent mechanisms of TRbeta-induced repression of transcription.
González-Manchón
C
C
Department of Pathophysiology and Human Molecular Genetics, Centro de Investigaciones Biológicas (CSIC), Velázquez 144, 28006, Madrid, Spain.
Ayuso
M S
MS
Parrilla
R
R
D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008291:Malate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D020218:Response Elements / Q000502:physiology*; D047488:Retinoid X Receptors; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000378:metabolism / Q000494:pharmacology
D004268:DNA-Binding Proteins; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014284:Triiodothyronine; D004247:DNA; D008291:Malate Dehydrogenase