Abstract 14257: Cell Type-Specific Decrease of Gene Body DNA Methylation Levels in Cardiomyocyte-Specific Genes Contribute to the Transcriptional Efficiency at Postnatal Development of Mouse Cardiomyocytes
[INTRODUCTION] Efficient and coordinated transcription of cardiomyocyte-specific genes is important throughout life for the maintenance of cardiomyocyte performance in response to diverse physiological stimuli. Mammalian genomic DNA is generally methylated in non-promoter regions, and DNA methylation in gene body regions restricts the transcriptional efficiency of genes.
[METHODS AND RESULTS] We analyzed the genome-wide transcription and DNA methylation status of purified mouse cardiomyocytes from several developmental stages using 1) expression microarray for transcription, 2) bisulfite sequencing, and 3) semi-quantitative high-throughput method by massive parallel sequencing for DNA methylation. The gene body DNA methylation levels of multiple cardiomyocyte-specific genes, including cardiac myosin heavy chain (MHC) and titin genes, showed a dynamic decrease in postnatal cardiomyocytes compared with embryonic ones. The simultaneous decline of DNA methylation, for example, in the entire 55 Kbp region of the MHC locus, is cell type- and locus-specific, and is not simply correlated with immediate transcriptional changes. This suggests that gene body DNA methylation levels of cardiomyocyte-specific genes are selectively modulated in cardiomyocytes before birth. Compared with other genes with similar features in their sequence context, gene structure and promoter DNA methylation status, the subset of cardiomyocyte-specific genes keeps higher transcriptional levels, implying that the low DNA methylation levels in their gene body regions facilitate higher transcription efficiency in postnatal cells. As gene body regions with higher transcriptional activity tend to be a target of DNA methylation in proliferating cells, the gene body DNA methylation status in cardiomyocytes is under a different regulation in both proliferating and non-proliferating cardiomyocytes.
[CONCLUSION] We concluded that the gene body DNA methylation of the cardiomyocyte-specific gene subpopulation was specifically altered during the postnatal stage. We propose that the epigenetic status of the cardiomyocyte-specific gene locus is advance-programmed for, and contributes to, the efficient transcription of the genes in maturated cardiomyocytes.
- © 2011 by American Heart Association, Inc.