Induction of the BCMO1 gene during the suckling-weaning transition in rats is associated with histone H3 K4 methylation and subsequent coactivator binding and histone H3 acetylation to the gene.

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.

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