OBJECTIVE: Histone methylation patterns are associated with various aspects of biology, including transcriptional regulation. Methylation of histone H3 at lysine 4 (H3K4) leads to transcriptional activation through recruitment of transcription activation complexes onto target genes; in contrast, methylation of histone H3K9, or histone H4K20, leads to transcriptional inactivation attracting heterochromatin protein 1 (HP1). It is not yet known whether jejunal induction of sucrase-isomaltase (Si) and sodium-dependent glucose cotransporter (Sglt1) genes by intake of a high-starch/low-fat diet in rats is regulated by coordinated changes of these histone methylation events. In the present study, we investigated whether these histone modifications at the promoter, enhancer, and transcribed regions of Si and Sglt1 genes in rat jejunum are affected by consumption of a high-starch/low-fat diet. METHODS: Chromatin immunoprecipitation assays using antibodies against methylated-histone H3K4, H3K9, H4K20, and HP1 were performed at various regions associated with the Si and Sglt1 genes in jejunum of rats fed a high-starch/low-fat diet or a low-starch/high-fat diet for 7 d. RESULTS: Feeding rats the high-starch/low-fat diet induced mono-, di-, and trimethylation of histone H3K4 on the promoter and transcribed regions of the Si and Sglt1 genes. In contrast, methylation of histones H3K9 and H4K20, and binding of HP1 at these gene regions, were not affected by the high-starch/low-fat diet. CONCLUSION: These observations suggest that induction of Si and Sglt1 gene expression in rat jejunum by a high-starch/low-fat diet intake is positively associated with histone H3K4 methylation, but not with histone H3K9/H4K20 methylation, or with binding of HP1.