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Hormone-induced Rat Atrial Natriuretic Factor Transcription in Cardiac Myocytes

出版	University of California, San Diego, 1994
URL	http://books.google.com.hk/books?id=VfQfCCc8MrwC&hl=&source=gbs_api

註釋Atrial natriuretic factor (ANF) is a cardiac-derived peptide hormone involved in hemodynamic balance and is a marker of the cardiac growth response. In primary myocardial cells the [alpha]1-adrenergic agonist, phenylephrine (PE), is a potent activator of ANF transcription; however, the cis-elements and trans-factors mediating this induction remain largely uncharacterized. A region of the rat ANF 5'-flanking sequence between -122 bp and -109 bp was shown to contain a minimal inducible element (MIE) required for full PE-inducible reporter expression. Electrophoretic mobility shift assays (EMSA) revealed the formation of two complexes between myocardial nuclear proteins and the MIE. Interference analyses indicated that complex 1 bound to an SRE-like region of the MIE, while complex 2 bound to a nearby GATA motif. Supershift EMSA demonstrated that the protein(s) comprising complex 1 crossreacted with antisera against human SRF, while protein(s) comprising complex 2 crossreacted with GATA-4 antisera. Point mutations in the MIE which disrupted SRF binding also blocked PE-inducible transcription, while mutations disrupting GATA protein binding had no effect. Additionally, EMSA suggested that myocardial cell SRF did not form a ternary complex and supershift analysis showed that myocardial cell SRF is phosphorylated on Ser-103; this modification is known to be required for SRF-inducible transcription in the absence of accessory factor-mediated ternary complex formation. These results, which are among the first which link SRF with hormone-inducible ANF transcription in primary cardiac myocytes, also establish a probable role for SRF in hormone-inducible transcription of other cardiac genes.