Transcriptional regulation of slc6a19 along the crypt-villus axis

Abstract

Digestion of proteins takes place mainly in the small intestine followed by the absorption of amino acids and peptides by enterocytes. The absorption surface area in the intestine is drastically increased by finger-like protrusions along the small intestinal lumen (called villi) and invaginations (called crypts). Enterocytes develop from stem cells in the crypt and differentiate into mature enterocytes while moving along the crypt–villus axis. The Slc6a19 mRNA and its resulting B0AT1 protein show a striking increase of expression towards the tip of the villi and are virtually absent in the crypts. In my PhD research, I investigated transcription factors and epigenetic modulators that regulate Slc6a19 expression. The Slc6a19 gene encodes the neutral amino acid transporter B0AT1, which provides the main mechanism of neutral amino acid absorption in the intestine. My experiments demonstrate that epigenetic modifications and transcription factor distribution orchestrate B0AT1 expression along the crypt–villus axis.