To better understand the reguratory mechanisms in gene expression of human
cardiomyocytes, we studied the expression of MEF2 genes encoding transcript
ion factors during the course of cardiac development. Expression of all fou
r MEF2 transcripts (MEF2A, MEF2B, MEF2C, and MEF2D) mere detected in all de
velopmental stage of the human heart, while Mef2b transcripts mere down-reg
ulated in mouse heart development. Although none of the MEF2 genes, besides
mouse Mef2b, exhibited any remarkable quantitative change in their transcr
ipts, qualitative changes in MEF2 transcripts were found during the course
of cardiac development. In particular, MEF2D transcripts showed prominent c
hanges by alternative splicing in the perinatal period. MEF2D transcripts c
ontaining the 21-base exon (exon b) were predominantly expressed after birt
h. At the same time, transcripts of the alpha myosin heavy chain (alpha MHC
) gene increased after birth, as the splicing pattern in transcripts of the
cardiac troponin T (cTnT) gene changed to decrease the transcripts of cTnT
1 after birth. These changes seemed to be correlated with the alternative s
plicing changes of MEF2 genes, especially MEF2D. The alternative splicing a
s well as transcriptional regulation in MEF2 genes might be important for r
egulating the alpha MHC gene and the maturation of cardiomyocytes. (C) 1999
Tohoku University Medical Press.