Demethylase Tet1-mediated DNA Demethylation Modification Regulates Heart Development And Function

Heart development is a complex process from embryo to adult,involving cell proliferation,migration,differerntiation,programmed cell death and structural remodeling.The normal development of the heart is an important basis for maintaining its basic functions.It is well-known that the development of the heart is influenced by many factors,including heredity,environment and epigenetics.Studies over the past few years have shown that epigenetic modifications play an important role in regulating heart development.Epigenetic mechanisms mainly include DNA methylation,chromatin remodeling and histone modifications and non-coding RNA.DNA methylation is the most extensive study of epigenetic modifications to influence heart development process.The process of DNA methylation(5-mc)to demethylation(5-hmc)is a new DNA epigenetic modification.It is mainly mediated by the TET(Ten-Eleven Translocation,TET)dioxygenase protein family(Tetl,Tet2,Tet3).In mammals,TET family proteins are involved in the regulation of multiple biological processes of heart development,afifecting the regulation of tissue-specific gene expression,cell development and genome stability,to ensure the normal structure and function of the heart in the body.This article focused on the effect of DNA demethylase Tetl-mediated DNA demethylation on heart development,structure and function.Cellular biology,immunohistochemistry,mouse cardiac ultrasound and high-throughput sequencing techniques were used to explore the regulatory role of Tetl involvement.We found that Tetl was continuously expressed in the heart during the entire development of the mouse.The expression level of Tetl protein was P1>P14>>P8W,and the expression level decreased significantly after adulthood.In all stages of heart development,the 5hmC modification in WT mice was significantly greater than KO mice.Through heart tissue staining of adult mouse,we found that P8W KO mice exhibited a certain degree of myocardial fibrosis and dilated heart chambers,whereas WT mice did not have this feature.Meanwhile,the results of mouse cardiac ultrasound showed that the contractile function of KO mice was lower than that of WT mice.To sum up,the results of the study showed that DNA demethylation mediated by the demethylase Tetl is involved in the regulation of cardiac development,which in turn affects the structure and function of the heart.