Estrogen modulation of apolipoprotein(a) expression. Identification of a regulatory element.
Elevated plasma levels of the lipoprotein particle Lp(a) are a major risk factor for cardiovascular disease. Lp(a) plasma levels are determined by the level of expression of its characteristic protein component, apo(a). Apo(a) expression is modulated by several hormones, of which estrogens are the best known. The chromosomal region responsible for estrogen response was identified within an apo(a) enhancer located at approximately 26 kilobases from the apo(a) promoter. Although the estrogen-responsive unit contains a potential estrogen response element, binding of estrogen receptor-alpha to DNA was not necessary. The receptor, activated by bound estradiol, interacts through its transactivation domains with a transcription factor necessary for the function of the enhancer, preventing its binding to DNA.
Boffelli
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D
Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, California 94305-5246, USA.
Zajchowski
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DA
Yang
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Z
Lawn
R M
RM
D001054:Apolipoproteins A / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D004742:Enhancer Elements, Genetic; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D008969:Molecular Sequence Data; D010958:Plasminogen / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D015533:Transcriptional Activation / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D001054:Apolipoproteins A; D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D004967:Estrogens; D011960:Receptors, Estrogen; D004958:Estradiol; D010958:Plasminogen