Isolation of a ventricle‐specific promoter for the zebrafish ventricular myosin heavy chain (<i>vmhc</i>) gene and its regulation by GATA factors during embryonic heart development

Park, Jae Sun; Kim, Hyung Seok; Kim, Jun Dae; Seo, Jooyeok; Chung, Kwansoo; Lee, Ho Sa; Huh, Tae Lin; Jo, Inho; Kim, Yong Ou

doi:10.1002/dvdy.21964

Cited by 15 publications

(9 citation statements)

References 38 publications

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“…Moreover, whole embryo knockouts of Gata4 demonstrated elevated levels of GATA6, suggesting an in vivo compensatory response (Molkentin et al, 1997). This redundancy has been shown in multiple developmental systems, and our results add coronary vasculogenesis to this roster (Park et al, 2009; Xin et al, 2006). …”

Section: Discussionsupporting

confidence: 79%

Epicardial GATA factors regulate early coronary vascular plexus formation

Kolander¹,

Holtz²,

Cossette³

et al. 2014

Developmental Biology

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During early development, GATA factors have been shown to be important for key events of coronary vasculogenesis, including formation of the epicardium. Myocardial GATA factors are required for coronary vascular (CV) formation; however, the role of epicardial localized GATAs in this process has not been addressed. The current study was conducted to investigate the molecular mechanisms by which the epicardium controls coronary vasculogenesis, focusing on the role of epicardial GATAs in establishing the endothelial plexus during early coronary vasculogenesis. To address the role of epicardial GATAs, we ablated GATA4 and GATA6 transcription factors specifically from the mouse epicardium and found that the number of endothelial cells in the sub-epicardium was drastically reduced, and concomitant coronary vascular plexus formation was significantly compromised. Here we present evidence for a novel role for epicardial GATA factors in controlling plexus formation by recruiting endothelial cells to the sub-epicardium.

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Section: Discussionsupporting

confidence: 79%

Epicardial GATA factors regulate early coronary vascular plexus formation

Kolander¹,

Holtz²,

Cossette³

et al. 2014

Developmental Biology

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“…In zebrafish, the lack of myh7 expression in the atrium is regulated by Nkx2.5 [134]. The zebrafish homeobox transcription factor Prx2 and the mouse Gata factors Gata4 and Gata6 have also been shown to regulate myh7 expression [131, 134, 135]. However, in embryonic hearts isolated from compound heterozygote Gata4/Tbx5 mice, mRNA expression of Myh7 was found to be unaffected, unlike Myh6 , which showed decreased expression in the compound heterozygote but not in the single Gata4 and Tbx5 heterozygotes [130].…”

Section: The Role Of Transcription Factors In the Regulation Of Myosinmentioning

confidence: 99%

Heavy and light roles: myosin in the morphogenesis of the heart

England

Loughna

2012

Cell. Mol. Life Sci.

173

136

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Myosin is an essential component of cardiac muscle, from the onset of cardiogenesis through to the adult heart. Although traditionally known for its role in energy transduction and force development, recent studies suggest that both myosin heavy-chain and myosin light-chain proteins are required for a correctly formed heart. Myosins are structural proteins that are not only expressed from early stages of heart development, but when mutated in humans they may give rise to congenital heart defects. This review will discuss the roles of myosin, specifically with regards to the developing heart. The expression of each myosin protein will be described, and the effects that altering expression has on the heart in embryogenesis in different animal models will be discussed. The human molecular genetics of the myosins will also be reviewed.

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“…For example, Nkx2-5 autoregulates its own transcription in the second heart field via conserved enhancers by combinatorial but not individual expression of Nkx2-5, SRF, GATA4, GATA6, myocardin, and p300 [57]. The Xenopus MLC2 gene contains GATA4 binding sites that flank a YY1/CarG-like site that mediate its myocardial expression [58] and the zebrafish ventricular myosin heavy chain ( vmhc ) promoter contains a proximal cardiac enhancer element with multiple NKEs and GATA factor binding sites upstream of an SRF binding site [59], both similar to the configuration observed in the DCE of Lrrc10 . In the case of Lrrc10 , the SRF binding site within the DCE is not critical for SRF-mediated activation, but SRF cooperates with Nkx2-5 and GATA4 (Fig 5B).…”

Section: Discussionmentioning

confidence: 99%

“…The expression of rat carnitine palmitoyltransferase Iβ [62] and human 5-hydroxytryptamine receptor 4 [63] is regulated by an enhancer element in the 5′UTR that contains putative overlapping NKE and GATA binding sites or a putative NKE, respectively. Zebrafish ventricular myosin heavy chain ( vmhc ) contains overlapping NKEs in the second intron [59, 64] that are functionally important in the regulation of ventricular specific expression [64]. Additionally, splice variants 1A and 1C of the mouse cardiac sodium channel ( Scn5a ) contain cardiac enhancer elements within the 5′UTR and within the first exon, respectively [65].…”

Section: Discussionmentioning

confidence: 99%

Lrrc10 is a novel cardiac-specific target gene of Nkx2-5 and GATA4

Brody

Cho

Mysliwiec

et al. 2013

Journal of Molecular and Cellular Cardiology

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Cardiac gene expression is precisely regulated and its perturbation causes developmental defects and heart disease. Leucine-rich repeat containing 10 (Lrrc10) is a cardiac-specific factor that is crucial for proper cardiac development and deletion of Lrrc10 in mice results in dilated cardiomyopathy. However, the mechanisms regulating Lrrc10 expression in cardiomyocytes remain unknown. Therefore, we set out to determine trans-acting factors and cis-elements critical for mediating Lrrc10 expression. We identify Lrrc10 as a transcriptional target of Nkx2-5 and GATA4. The Lrrc10 promoter region contains two highly conserved cardiac regulatory elements, which are functional in cardiomyocytes but not in fibroblasts. In vivo, Nkx2-5 and GATA4 endogenously occupy the proximal and distal cardiac regulatory elements of Lrrc10 in the heart. Moreover, embryonic hearts of Nkx2-5 knockout mice have dramatically reduced expression of Lrrc10. These data demonstrate the importance of Nkx2-5 and GATA4 in regulation of Lrrc10 expression in vivo. The proximal cardiac regulatory element located at around −200 bp is synergistically activated by Nkx2-5 and GATA4 while the distal cardiac regulatory element present around −3 Kb requires SRF in addition to Nkx2-5 and GATA4 for synergistic activation. Mutational analyses identify a pair of adjacent Nkx2-5 and GATA binding sites within the proximal cardiac regulatory element that are necessary to induce expression of Lrrc10. In contrast, only the GATA site is functional in the distal regulatory element. Taken together, our data demonstrate that the transcription factors Nkx2-5 and GATA4 cooperatively regulate cardiac-specific expression of Lrrc10.

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Isolation of a ventricle‐specific promoter for the zebrafish ventricular myosin heavy chain (vmhc) gene and its regulation by GATA factors during embryonic heart development

Cited by 15 publications

References 38 publications

Epicardial GATA factors regulate early coronary vascular plexus formation

Epicardial GATA factors regulate early coronary vascular plexus formation

Heavy and light roles: myosin in the morphogenesis of the heart

Lrrc10 is a novel cardiac-specific target gene of Nkx2-5 and GATA4

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