Mechanisms underlying generation of gradients in gene expression within the intestine: an analysis using transgenic mice containing fatty acid binding protein-human growth hormone fusion genes

Genes Dev. 1988 Oct;2(10):1318-32. doi: 10.1101/gad.2.10.1318.

Abstract

The intestine is lined by a continuously regenerating epithelium that maintains gradients in 'liver' fatty acid binding protein (L-FABP) gene expression along its horizontal and vertical axes, i.e., from duodenum to colon and from crypt to villus tip. To identify cis-acting DNA sequences responsible for these regional differences, we linked portions of the L-FABP gene's 5' nontranscribed region to the human growth hormone (hGH) gene and examined hGH expression in transgenic mice. Nucleotides -596 to +21 of the rat L-FABP gene correctly directed hGH expression to enterocytes and hepatocytes. However, anomalous expression was observed in small intestinal crypts, colon, and renal proximal tubular epithelial cells. Addition of nucleotides -4000 to -597 of the L-FABP gene, in either orientation, suppressed renal hGH expression and restored a nearly normal horizontal, but not a vertical, hGH gradient in the intestine. Thus, horizontal gradients of gene expression within the intestine can be maintained by orientation-independent, cis-acting suppressor elements.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics*
  • Cloning, Molecular*
  • Epithelium / metabolism
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • Growth Hormone / biosynthesis
  • Growth Hormone / blood
  • Growth Hormone / genetics*
  • Humans
  • Immunoblotting
  • Immunoenzyme Techniques
  • Intestinal Mucosa / metabolism*
  • Kidney Tubules, Proximal / metabolism
  • Liver / metabolism
  • Mice
  • Mice, Transgenic
  • Mosaicism
  • Neoplasm Proteins*
  • Nerve Tissue Proteins*
  • Nucleic Acid Hybridization
  • Organ Specificity
  • Promoter Regions, Genetic
  • RNA / biosynthesis
  • Radioimmunoassay
  • Regulatory Sequences, Nucleic Acid*
  • Restriction Mapping
  • Tumor Suppressor Proteins*

Substances

  • Carrier Proteins
  • FABP1 protein, human
  • FABP7 protein, human
  • Fabp1 protein, mouse
  • Fabp1 protein, rat
  • Fabp5 protein, mouse
  • Fabp7 protein, mouse
  • Fabp7 protein, rat
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Tumor Suppressor Proteins
  • RNA
  • Growth Hormone