The cells involved in nutrient absorption in the small intestine of rats undergo rapid maturation during the suckling-weaning transition period, i.e., 2-4 wk after birth. During this period, the serum thyroid hormone level is increased. However, the molecular mechanisms involved in the regulation of β-carotene 15,15'-monooxygenase 1 (BCMO1) gene expression in the small intestine remain unknown. In this study, we found that jejunal β-carotene 15,15' dioxygenase activity and the gene expression of BCMO1 were significantly increased during this transition period between days 13 and 27 after birth. A chromatin immunoprecipitation assay revealed that di- and tri-methylation of histone H3 at lysine 4 (K4) and the binding of thyroid hormone receptor (TR) α-1 binding on the promoter/enhancer and/or transcribed regions of the BCMO1 gene were enhanced from the earlier stage of weaning (i.e., 20 d after birth), prior to an enhancement of the acetylation of histone H3 and the binding of coactivator (SRC-1 and CBP) to the promoter/enhancer and/or transcribed regions of the BCMO1 gene, which was apparent at 27 d after birth. These results suggest that histone H3 K4 methylation and TRα-1 binding on the BCMO1 gene during the suckling-weaning transient period in rats predisposes to subsequent coactivator recruitment and histone H3 acetylation on the gene.