Epicardium-Derived Tbx18+ CDCs Transplantation Improve Heart Function in Infarcted Mice

Guo, Zhan; Geng, Mengyuan; Qin, Litao; Hao, Bingtao; Liao, Shixiu

doi:10.3389/fcvm.2021.744353

Cited by 3 publications

(1 citation statement)

References 51 publications

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“…It was predicted that variant g.4716G>A may attenuate the bindings of TBX1 , TBX4 , TBX6 , TBX15 and TBX18 to the promoter region of the MYH6 gene. In fact, these genes are differentially expressed at various stages of heart development, participating in the formation of the heart [ 42 – 46 ]. In summary, the variants in the promoter of MYH6 gene identified in this study may modify the TFBS clusters in the promoter and interfere with the formation of transcriptional regulatory complexes with related TFs, leading to the formation of VSD.…”

Section: Discussionmentioning

confidence: 99%

Identification and functional analysis of variants of MYH6 gene promoter in isolated ventricular septal defects

et al. 2022

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Background Ventricular septal defect is the most common form of congenital heart diseases. MYH6 gene has a critical effect on the growth and development of the heart but the variants in the promoter of MYH6 is unknown. Patients and methods In 604 of the subjects (311 isolated and sporadic ventricular septal defect patients and 293 healthy controls), DNA was extracted from blood samples and MYH6 gene promoter region variants were analyzed by sequencing. Further functional verification was performed by cellular experiments using dual luciferase reporter gene analysis, electrophoretic mobility shift assays, and bioinformatics analysis. Results Nine variants were identified in the MYH6 gene promoter and two of those variants [g.4085G>C(rs1222539675) and g.4716G>A(rs377648095)] were only found in the ventricular septal defect patients. Cellular function experiments showed that these two variants reduced the transcriptional activity of the MYH6 gene promoter (p < 0.001). Further analysis with online JASPAR database suggests that these variants may alter a set of putative transcription factor binding sites that possibly lead to changes in myosin subunit expression and ventricular septal defect formation. Conclusions Our study for the first time identifies variants in the promoter region of the MYH6 gene in Chinese patients with isolated and sporadic ventricular septal defect. These variants significantly reduced MYH6 gene expression and affected transcription factor binding sites and therefore are pathogenic. The present study provides new insights in the role of the MYH6 gene promoter region to better understand the genetic basis of VSD formation.

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Section: Discussionmentioning

confidence: 99%