A new function of DNA methylation----Regulating gene expression in human heart failure

DNA methylation is an epigenetic mechanism which is important in normal organismal development and cellular differentiation in higher organisms. At present, it is discovered that DNA methylation responses to differential gene expression in cells, suppressing expression of viral genes and other deleterious elements and forming of chromatin structure. Additionally, it even play a crucial role in the development of almost all types of cancer. However, it is still unknown that whether the differential DNA methylation correlates with the differential gene expression of Angiogenic factors in Human Heart failure, in spite of the ascertain that other epigenetic mechanisms, such as microRNA and histone modification, which are responsible in this issue.

For comparing ischaemic and idiopathic end-stage cardiomyopathic left ventricular with normal control, Mehregan Movassagh and colleagues performed a preliminary analysis using methylated-DNA immunoprecipitation-chip, validated differential methylation loci by bisulfite-PCR and high throughput sequencing, and identified three gene regions in angiogenic family which can be regulated by DNA methylation, AMOTL2, ARHGAP24, and PECAM1.
Using quantitative RT-PCR and associating with previous study, they found that the genes expression differed significantly between cardiomyopathic hearts and normal control. Shown below:
1 Hypermethylation in the 5’ region of PECAM1 (DMR11) in dilated hearts correlated with decreased expression of PECAM1.
2 Hypomethylation within the gene body of AMOTL2 (DMR24) correlated with reduced expression of AMOTL2.
3 Hypermethylation within the gene body of ARHGAP24 (DMR36) correlated with increased expression of ARHGAP24.
Thus, we can confirm that the differential DNA methylation exists in human cardiomyopathy and it regulates the differential gene expression.

However, we still have to make more effort to investigate more correlated gene regions and unravel the interaction between DNA methylation and special DNA-binding protein regulatory. Moreover, the link between DNA methylation variation and other complex diseases also need to be unravelled.

Reference
Movassagh M, Choy MK, Goddard M, Bennett MR, Down TA, Foo RS. 2010. Differential DNA methylation correlates with differential expression of angiogenic factors in human heart failure. PLoS One 5: e8564

Zhengyang Zhao
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