Complex interactions among tissue restricted transcription factors and cofactors are critical for intestine specific gene expression

Abstract

As might be concluded from the general introduction about gene regulation, our understanding of how transcription factors regulate transcription ofLPH and SI is extensive. Both LPH and SI are enterocyte specific membrane anchored enzymes that are necessary for the digestion of nutrients present in the specific diets of mammals according to their age before and after weaning. Previous work by Grand et. al. has demonstrated that LPH and SI are expressed in complex patterns along the vertical, horizontal, and developmental gradient of the small intestine. LPH and SI expression patterns coincide with important transitions during small intestine development. Furthermore, Krasinski et. al. demonstrated that specific regions in the LPH promoter contain the information necessary for the specific patterns of expression. Krasinski et. al also demonstrated that the vertical, horizontal, and developmental LPH and SI expression patterns are regulated at the level of transcription. Therefore, LPH and SI genes are perfect markers for cell differentiation of small intestine. Seqeunce analysis of the 5 '-flanking regions ofLPH and SI genes revealed consensus binding sites for Cdx-2, HNF-1, and GATA transcription factors. The families of these transcription factors have all been indicated to play a role in cell differentiation and morphogenesis. These transcription factors are turned on in early stages of intestinal development, are only expressed together in the small intestine, and their binding sites are in close proximity to each other and the TAT A-box regions suggesting that they play an important role in cell differentiation and intestine specific gene regulation. The close proximity of these binding sites to each other and the fact that these transcription factors have been shown individually to cooperate with comparable proteins for the regulation of gene expression, it is hypothesized that these factors act in concert to regulate LPH and SI transcriptio