Transcription elongation factor Brd4-P-TEFb accelerates intestinal differentiation-associated SLC2A5 gene expression

Expression of the fructose transporter gene SLC2A5 and histone acetylation in the transcribed region are induced by differentiation associated-signals such as glucocorticoids and p44/42 mitogen-activated protein kinase (MAPK) inhibition in small intestinal Caco-2 cells.

Brd4-P-TEFb plays a crucial role in differentiation-associated transcription of SLC2A5 gene in intestinal Caco-2 cells and in the small intestine of mice during weaning period. General significance: Histone acetylation and the transcription elongation factor Brd4 are important for SLC2A5 expression in the small intestine.

We co-treated with glucocorticoid receptor agonist dexamethasone (Dex) and p44/42 MAPK inhibitor PD98059 (PD) in Caco-2 cells with or without Brd4 small hairpin (sh) RNA expression vector, and the cells were analyzed by qRT-PCR and chromatin immunoprecipitation assays. The small intestine of wild-type mice and Brd4+/- mice during weaning period were analyzed by qRT-PCR.

Co-treatment with Dex and PD increased binding of the bromodomain-containing protein-4 (Brd4)-positive transcriptional elongation factor-b (P-TEFb)-RNA polymerase II complex to acetylated histones in the transcribed region of SLC2A5. Brd4-protein depletion by shRNA revealed that the association of these proteins on the transcribed region of SLC2A5 promoted gene expression in a Brd4-dependent manner. Expression of small-intestine Slc2a5, but not another intestinal gene sucrase-isomaltase, during weaning period, was significantly lower in Brd4+/- mice compared with wild-type mice. Conclusions: Brd4-P-TEFb plays a crucial role in differentiation-associated transcription of SLC2A5 gene in intestinal Caco-2 cells and in the small intestine of mice during weaning period. General significance: Histone acetylation and the transcription elongation factor Brd4 are important for SLC2A5 expression in the small intestine.

Histone acetylation and the transcription elongation factor Brd4 are important for SLC2A5 expression in the small intestine.