Role of histone acetylation in developmental regulation of rat GLUT5 in vivo

Abstract

In suckling mammals, expression of the intestinal fructose (F) transporter GLUT5 is low and cannot be stimulated by dietary F. When rats wean at ~14 d of age, GLUT5 transcription can be enhanced by F, indicating that regulation of GLUT5 is age‐sensitive. Histone H3 acetylation has previously been associated with transcriptional activation of GLUT5 in Caco2 cells. We perfused intestines of 10 and 20 d old rats either F or glucose (G), then determined levels of acetylation by ChIP assays using antibodies against acetylated histones H3 and H4. We used primer pairs targeting promoter regions 0 to ‐5100 bp upstream of the start site. GLUT5 expression and fructose uptake were similar among G‐ and F‐perfused intestines of 10 d and of G‐perfused 20 d olds but increased in F‐perfused intestines of 20 d olds. Histone H3 acetylation was clearly enhanced by F perfusion, but only in 20 d old rats. Increased H3 acetylation by F affected the downstream (‐1200 to 0) more than the upstream (‐5100 to ‐1400 bp) promoter regions. Likewise, histone H4 acetylation occurred only in F‐perfused intestines of 20 d olds. However, levels of H4 were lower than those of H3 acetylation and were evenly distributed between regions ‐5100 and 0 bp. F perfusion had no effect on H3 and H4 acetylation of GLUT5 in 10 d olds. Age‐dependent, F‐induced activation of GLUT5 transcription in vivo may be linked to age‐dependent factors modulating histone acetylation. (NSF722365)