DNA Methylation Profiling of the Fibrinogen Gene Landscape in Human Cells and during Mouse and Zebrafish Development
Figure 5
A model of changes in epigenetic marks and expression of fibrinogen genes during development.
A single fibrinogen gene is shown here to represent the three vertebrate fibrinogen chain genes and the model represents an average situation in a population of cells. An upstream promoter (P) and an intergenic liver enhancer (E) sequence are also represented. Prior to hepatocyte differentiation, CpGs in the fibrinogen genes are methylated (“me”) both in regulatory sequences and across the gene bodies. Embryonic hepatocytes show similar CpG methylation patterns, but with the expression of hepatocyte transcription factors (hep TFs) regulatory sequences are employed and fibrinogen mRNA expression is measurable. The H3K4me3 histone mark is also detectable near the gene promoters (grey cylinders). In later embryonic hepatocytes, expression of fibrinogen is clearly increased (red arrow), the H3K4me3 mark is more abundant at promoters and CpG methylation is moderately reduced, perhaps as a result of the loss of repressive CpG methylation upon cell division. In adult hepatocytes expression is marginally higher still, but CpG methylation is markedly reduced, in gene bodies and regulatory elements.