AIM: To investigate the role of epigenetic modification in Pdx-1 gene transcription and expression, and to compare the differences between epigenetic modifications of Pdx-1 gene promoter in various cell types of mice. METHODS: The promoter DNA methylation and histone modification status of Pdx-1 and MLH1 genes in NIT-1 cells, NIH3T3 cells and mouse embryonic stem cells were measured by chromatin immunoprecipitation-real time PCR method. The expression levels of these genes in the three cell lines were measured by real time RT-PCR. The relation between epigenetic modifications and gene expression was analyzed. RESULTS: (1) Compared to mES cells, there was lower DNA methylation and higher H3K4m3 modification levels in the promoter of Pdx-1 gene in NIT-1 cells (P<0.05). DNA methylation, H3 acetylation, H3K4m3 and H3K9m3 modification levels in the promoter of Pdx-1 gene in NIH3T3 cells were distinctly increased (P<0.05). (2) Pdx-1 gene transcription expressed only in NIT-1 cells. The Spearman's rho between Pdx-1 gene expression and DNA methylation (r=-0.802,P<0.01) was observed. The Pearson correlation between Pdx-1 gene expression and H3K4m3 modification (r=0.997,P<0.01) was also found. The Spearman's rho between Pdx-1 gene expression and H3K9m3 modification (r=-0.879,P<0.01) was observed. (3) No correlation between housekeeper MLH1 gene expression and epigenetic modification was found. CONCLUSION: DNA methylation, H3K4m3 and H3K9m3 modification coordinated participate to regulate and control the expression of Pdx-1 gene. It is of great significance to the differentiation of β cells from ES cells.