Sp3 inhibits Sp1-mediated activation of the cardiac troponin T promoter and is downregulated during pathological cardiac hypertrophy in vivo

American Journal of Physiology. Heart and Circulatory Physiology
Anthony AzakieYouping He

Abstract

Combinatorial interactions between cis elements and trans-acting factors are required for regulation of cardiac gene expression during normal cardiac development and pathological cardiac hypertrophy. Sp factors bind GC boxes and are implicated in recruitment and assembly of the basal transcriptional complex. In this study, we show that the cardiac troponin T (cTnT) promoter contains a GC box that is necessary for basal and cAMP-mediated activity of cTnT promoter constructs transfected in embryonic cardiomyocytes. Cardiac nuclear proteins bind the cTnT GC box in a sequence-specific fashion and consist of Sp1, Sp2, and Sp3 protein factors. By chromatin immunoprecipitation, Sp1 binds the cTnT promoter "in vivo." Cotransfected Sp1 trans-activates the cTnT promoter in cardiomyocytes in culture. Sp3 represses Sp1-mediated transcriptional activation of the cTnT gene in embryonic cardiomyocytes. Sp3 repression of Sp1-mediated cTnT promoter activation is dose dependent, inferring a mechanism of competitive binding/inhibition. To evaluate the role of Sp factors in cardiac gene expression in vivo, we have established a clinically relevant animal model of pathological cardiac hypertrophy where the fetal cardiac program is activated. In thi...Continue Reading

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Citations

Nov 3, 2010·Protein Expression and Purification·Cha-Jang LinTzu-Fun Fu
Dec 5, 2006·The Journal of Thoracic and Cardiovascular Surgery·Anthony AzakieYouping He
Sep 30, 2010·Journal of Cellular and Molecular Medicine·Xiaoqing HuChunyan Zhou
Feb 26, 2013·The Journal of Thoracic and Cardiovascular Surgery·Anthony AzakieYouping He
Jun 16, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Rebecca Johnson KamenyJeffrey R Fineman
Oct 31, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·Wendy K SteagallJoel Moss
Oct 6, 2020·Frontiers in Cell and Developmental Biology·Teng WuYong Xu
May 3, 2015·American Journal of Physiology. Heart and Circulatory Physiology·Rebecca Johnson KamenyJeffrey R Fineman
Aug 10, 2016·Clinical Science·Ursula Paula Renó SociEdilamar Menezes de Oliveira

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