Combinatorial interactions regulating cardiac transcription

Durocher, Daniel; Nemer, Mona

doi:10.1002/(sici)1520-6408(1998)22:3<250::aid-dvg7>3.0.co;2-5

Cited by 96 publications

(34 citation statements)

References 61 publications

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“…Studies (20,30,35) have shown that in response to volume overload or hypertrophic stimuli, the production of these natriuretic peptides in cardiomyocytes are greatly enhanced. The increased expression of ANP and BNP has been attributed mainly to the enhanced synthesis and release of these natriuretic peptides in cardiomyocytes (8,22). Our recent identification of corin as the pro-ANP convertase suggests that the activation of pro-ANP and pro-BNP could also be a critical step in the regulation of ANP and BNP production.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of corin gene expression in hypertrophic cardiomyocytes and failing myocardium

Tran¹,

Lu²,

Lei³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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High levels of plasma atrial natriuretic peptides (ANP) are associated with pathological conditions such as congestive heart failure (CHF). Recently, we have identified a cardiac serine protease, corin, that is the pro-ANP convertase. In this study, we examined the regulation of corin gene expression in cultured hypertrophic cardiomyocytes and in the left ventricular (LV) myocardium of a rat model of heart failure. Quantitative RT-PCR analysis showed that both corin and ANP mRNA levels were significantly increased in phenylephrine (PE)-stimulated rat neonatal cardiomyocytes in culture. The increase in corin mRNA correlated closely with the increase in cell size and ANP mRNA expression in the PE-treated cells (r = 0.95, P < 0.01; r = 0.92, P < 0.01, respectively). The PE-treated cardiomyocytes had an increased activity in converting recombinant human pro-ANP to biologically active ANP, as determined by a pro-ANP processing assay and a cell-based cGMP assay. In a rat model of heart failure induced by ligation of the left coronary artery, corin mRNA expression in the noninfarcted LV myocardium was significantly higher than that of control heart tissues from sham-operated animals, when examined by Northern blot analysis and RT-PCR at 8 wk. These results indicate that the corin gene is upregulated in hypertrophic cardiomyocytes and failing myocardium. Increased corin expression may contribute to elevation of ANP in the setting of cardiac hypertrophy and heart failure.

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Section: Discussionmentioning

confidence: 99%

Upregulation of corin gene expression in hypertrophic cardiomyocytes and failing myocardium

Tran¹,

Lu²,

Lei³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…2,15,21,22 Many reports have concluded that these transcription factors must interact physically for activation or repression of transcription to occur, and they have identified the homeodomain from the NK family of proteins, the C-terminal zinc finger of GATA-4, and the T-box of Tbx proteins as the domains mediating these protein-protein interactions. 17,[23][24][25][26][27] The importance of direct transcription factor interactions involving T-box factors in the cardiac gene regulatory network is underscored by the observation that mutations in Tbx5, causative for Holt-Oram syndrome, interrupt the binding of Tbx5 with GATA4. 28 Tbx20 is a cardiac T-box factor that is essential for heart morphogenesis and chamber muscle formation and acts to repress the expression of Tbx2 in developing chambers.…”

Section: Introductionmentioning

confidence: 99%

Conformational Stability and DNA Binding Specificity of the Cardiac T-Box Transcription Factor Tbx20

Macindoe¹,

Glockner²,

Vukasin³

et al. 2009

Journal of Molecular Biology

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“…In transactivation assays, it has been shown to act individually as a modest transcriptional activator of reporter genes carrying multimerized NKE binding sites (32). However, its transactivation capability is dramatically enhanced by association with other factors, including GATA-4 (33)(34)(35). As in the case of the GATA genes, there may be some functional redundancy in vertebrates between Nkx 2.5 and other members of the Nkx-2 family that are also expressed in heart, such as Nkx 2.3 (36).…”

Section: Introductionmentioning

confidence: 99%

GATA Factors Lie Upstream of Nkx 2.5 in the Transcriptional Regulatory Cascade That Effects Cardiogenesis

Brewer

Alexandrovich

Mjaatvedt

et al. 2005

Stem Cells and Development

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Members of the GATA-4, -5, and -6 subfamily of transcription factors are co-expressed with the homeoprotein Nkx 2.5 in the precardiac mesoderm during the earliest stages of its specification and are known to be important determinants of cardiac gene expression. Ample evidence suggests that GATA factors and Nkx 2.5 cross-regulate each other's expression; however, the temporal order of the expression of these transcription factors in vivo remains unresolved, and thus precise definition of the role of the products of the genes they transcribe in early development has been difficult to assess. We employed P19 CL6 mouse embryonic carcinoma cells as a model to investigate this problem, because these cells, like embryonic stem cells, can be induced to differentiate along multiple lineages. Here we demonstrate that when P19 CL6 cells are induced to differentiate to a cardiogenic lineage, the expression of GATA-4 and GATA-6 is up-regulated prior to the transcriptional activation of Nkx 2.5. Moreover, over-expression of GATA-4 or -6 at the time of Nkx 2.5 induction results in a significant up-regulation of endogenous Nkx 2.5 transcription. Finally, it is known that a Nkx-dependent enhancer is necessary for GATA-6 expression within cardiomyocytes of the developing mouse embryo. We demonstrate that within undifferentiated P19 CL6 cells, GATA-6 expression is subject to active repression by a novel upstream element that possesses binding sites for factors involved in transcriptional repression that are conserved between mammalian species.

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Combinatorial interactions regulating cardiac transcription

Cited by 96 publications

References 61 publications

Upregulation of corin gene expression in hypertrophic cardiomyocytes and failing myocardium

Upregulation of corin gene expression in hypertrophic cardiomyocytes and failing myocardium

Conformational Stability and DNA Binding Specificity of the Cardiac T-Box Transcription Factor Tbx20

GATA Factors Lie Upstream of Nkx 2.5 in the Transcriptional Regulatory Cascade That Effects Cardiogenesis

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