Figure 6
A model for FBN1 gene regulation by varied DNA methylation of the CpG island shore of FBN1 het KO cells/tissues. In the FBN1 het KO cells and tissues, the amount of functional FBN1 mRNA is regulated by DNA methylation status within the FBN1 CpG island shore of the WT allele. The null KO allele does not contribute any FBN1 function because the FBN1 preRNA includes a premature stop codon and degraded after splicing coupled with translational initiation. The WT allele is hypomethylated in het KO cells and therefore, the total amount of the functional FBN1 mRNA is sufficient in tissue (cell population), regardless of the methylation status of the KO allele (left panel). In contrast, the WT allele is hypermethylated and functional FBN1 mRNA is not sufficiently transcribed in the tissue or cell population (right panel). Open and closed circles represent unmethylated and methylated CpGs within the FBN1 CpG island shore, respectively; while black and white circles indicate either methylated or unmethylated CpGs. White and gray squares represent WT and KO alleles of FBN1, respectively.
