Temporal regulation of p300 on heart-specific transcription factors during mouse cardiogenesis / 重庆医科大学学报

ABSTRACT

Objective:Cardiogenesis is a precise process controlled by sequential gene regulatory steps.Heart-specific transcription factors (TFs)GATA4,Nkx2.5,MEF2C and Tbx5 play critical roles in controlling heart development.But the genetic basis for the temporal expression of genes during heart development still remains unclear.Substantial studies displayed gene regulation partly attributes to histone acetylation.However,the functions of individual histone acetyltransferases (HATs)in specific developmental transcription programs are not well elucidated.p300,a histone acetyltransferase and coactivator,plays key role in many physiological processes,moreover our previous study suggests that expression of p300 is developmentally regulated during mouse cardiogenesis,but the underlying molecular mechanism remains elusive.Methods:The whole hearts from embryonic mice on embryonic days (E)10.5 and 16.5 were collected accordingly,and then total RNA was extracted.Heart-specific TFs GATA4,Nkx2.5,MEF2C and Tbx5 mRNA from mouse myocardium at differential embryonic days during cardiac development were analyzed by quantitative (Q)-PCR.The levels of histone H3 acetylation on these heart-specific TFs promoter and transcription factor binding sites of p300 to these genes were identified by chromatin immunoprecipitation assays (ChIP).Results:The present study furnishes a comparative temporal expression map of cardiac transcriptional factors,during murine heart development (E10.5 and E16.5).The mRNA levels of these genes present dynamic change.On E10.5,the expressions of GATA4 and MEF2C were remarkable lower than those on E16.5 (P