Elucidating the mechanisms of transcription regulation during heart development by next-generation sequencing

Nimura, Keisuke; Kaneda, Yasufumi

doi:10.1038/jhg.2015.84

Cited by 3 publications

(3 citation statements)

References 104 publications

(134 reference statements)

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“…GATA4 is a cardiac transcription factor required for cardiac development. GATA4 interacts with other transcription factors, including NKX2.5, TBX5, and MEF2A to regulate heart development and gene expression (Nimura and Kaneda, 2016 ). While GATA4 knockdown is embryolethal, mutations of GATA4 are associated with cardiac septal defects as well as pulmonary stenosis (Garg et al, 2003 ; Tomita-Mitchell et al, 2007 ; McCulley and Black, 2012 ; Misra et al, 2012 ), but also with tetralogy of Fallot (TOF) and double outlet right ventricle (DORV) (Andersen et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

“…While GATA4 knockdown is embryolethal, mutations of GATA4 are associated with cardiac septal defects as well as pulmonary stenosis (Garg et al, 2003 ; Tomita-Mitchell et al, 2007 ; McCulley and Black, 2012 ; Misra et al, 2012 ), but also with tetralogy of Fallot (TOF) and double outlet right ventricle (DORV) (Andersen et al, 2014 ). TEAD1 (TEA domain family member 1, also known as transcriptional enhancer factor 1, TEF-1), a cardiac transcription factor that regulates muscle gene expression, interacts with GATA4 and other transcription factors, including NKX2.5 (He et al, 2011 ; Nimura and Kaneda, 2016 ). In addition, CTNNB1 (a downstream component of the Wnt signaling pathway) encodes a protein that forms adherens junctions, and thus is necessary for the creation and maintenance of epithelial and endothelial cell layers.…”

Section: Discussionmentioning

confidence: 99%

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Increased Hemodynamic Load in Early Embryonic Stages Alters Endocardial to Mesenchymal Transition

et al. 2017

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Normal blood flow is essential for proper heart formation during embryonic development, as abnormal hemodynamic load (blood pressure and shear stress) results in cardiac defects seen in congenital heart disease. However, the progressive detrimental remodeling processes that relate altered blood flow to cardiac defects remain unclear. Endothelial–mesenchymal cell transition is one of the many complex developmental events involved in transforming the early embryonic outflow tract into the aorta, pulmonary trunk, interventricular septum, and semilunar valves. This study elucidated the effects of increased hemodynamic load on endothelial–mesenchymal transition remodeling of the outflow tract cushions in vivo. Outflow tract banding was used to increase hemodynamic load in the chicken embryo heart between Hamburger and Hamilton stages 18 and 24. Increased hemodynamic load induced increased cell density in outflow tract cushions, fewer cells along the endocardial lining, endocardium junction disruption, and altered periostin expression as measured by confocal microscopy analysis. In addition, 3D focused ion beam scanning electron microscopy analysis determined that a portion of endocardial cells adopted a migratory shape after outflow tract banding that is more irregular, elongated, and with extensive cellular projections compared to normal cells. Proteomic mass-spectrometry analysis quantified altered protein composition after banding that is consistent with a more active stage of endothelial–mesenchymal transition. Outflow tract banding enhances the endothelial–mesenchymal transition phenotype during formation of the outflow tract cushions, suggesting that endothelial–mesenchymal transition is a critical developmental process that when disturbed by altered blood flow gives rise to cardiac malformation and defects.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Increased Hemodynamic Load in Early Embryonic Stages Alters Endocardial to Mesenchymal Transition

et al. 2017

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“…If the TBX5 expressing region is misplaced, the ventricular septal is formed in this new region. Also, TBX5 is important in the formation of upper human organs and its mutation causes Holt-Oram syndrome (HOS) (Basson et al, 1999;Nimura & Kaneda, 2016). Thus, the transcription factor of the homeobox TBX5, expressed during heart formation, acts as an important regulator and plays a vital role in activating the genes which cooperate in the formation of the right and left heart (Fujita et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Novel mutations A210G and L15Q TBX5 gene in the patients with non-syndromic congenital defects of the heart septal

Soheili

Vilmundarson

Jalili

2020

Preprint

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The TBX5 transcription factor plays an important role during morphogenesis and development of the heart. Mutations in this gene often lead to Holt-Oram syndrome (HOS). This study identified mutations in patients with non-syndromic congenital heart defects (CHD). Screening for mutations TBX5 gene in non-syndromic CHD, including 100 patients with a septal defect and 50 healthy subjects as controls were performed by the technique of high-resolution melt (HRM). Exons were sequenced for samples that showed HRM curve differences compared to controls. Structural stability and pathogenic potential of mutated protein were evaluated by bioinformatics analysis. HRM curve analysis showed that the curves of three samples deviated from the curves of controls. Sequencing showed three heterozygous missense mutations including two novel mutations NM-000192.3:c.44T>G, (p.L15Q), NM 000192.3c.629C>G (p.A210G) and a known mutation NM 000192.3:c.331G>T (p.D111Y). The PolyPhen-2 software predicted the p.D111Y and p.A210G substitutions to be disease-causing and p.L15Q as possibly benign, while protein structural stability analysis by MUpro and DynaMut suggested that these mutations reduce stability and increase the flexibility of the protein. This study presents two novel missense mutations within the TBX5 gene that may be causal for non-syndrome CHD.

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Myocardial transcription factors in diastolic dysfunction: clues for model systems and disease

Михайлов

Torrado

2016

Heart Fail Rev

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There are multiple intrinsic mechanisms for diastolic dysfunction ranging from molecular to structural derangements in ventricular myocardium. The molecular mechanisms regulating the progression from normal diastolic function to severe dysfunction still remain poorly understood. Recent studies suggest a potentially important role of core cardio-enriched transcription factors (TFs) in the control of cardiac diastolic function in health and disease through their ability to regulate the expression of target genes involved in the process of adaptive and maladaptive cardiac remodeling. The current relevant findings on the role of a variety of such TFs (TBX5, GATA-4/6, SRF, MYOCD, NRF2, and PITX2) in cardiac diastolic dysfunction and failure are updated, emphasizing their potential as promising targets for novel treatment strategies. In turn, the new animal models described here will be key tools in determining the underlying molecular mechanisms of disease. Since diastolic dysfunction is regulated by various TFs, which are also involved in cross talk with each other, there is a need for more in-depth research from a biomedical perspective in order to establish efficient therapeutic strategies.

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Elucidating the mechanisms of transcription regulation during heart development by next-generation sequencing

Cited by 3 publications

References 104 publications

Increased Hemodynamic Load in Early Embryonic Stages Alters Endocardial to Mesenchymal Transition

Increased Hemodynamic Load in Early Embryonic Stages Alters Endocardial to Mesenchymal Transition

Novel mutations A210G and L15Q TBX5 gene in the patients with non-syndromic congenital defects of the heart septal

Myocardial transcription factors in diastolic dysfunction: clues for model systems and disease

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