• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of biochemjBJ Latest papers and much more!
Biochem J. Mar 15, 1997; 322(Pt 3): 833–838.
PMCID: PMC1218263

Regulation of lactase-phlorizin hydrolase gene expression by the caudal-related homoeodomain protein Cdx-2.


Lactase-phlorizin hydrolase is exclusively expressed in the small intestine and is often used as a marker for the differentiation of enterocytes. The cis-element CE-LPH1 found in the lactase-phlorizin hydrolase promoter has previously been shown to bind an intestinal-specific nuclear factor. By electrophoretic mobility-shift assay it was shown that the factor Cdx-2 (a homoeodomain-protein related to caudal) binds to a TTTAC sequence in the CE-LPH1. Furthermore it was demonstrated that Cdx-2 is able to activate reporter gene transcription by binding to CE-LPH1. A mutation in CE-LPH1, which does not affect Cdx-2 binding, results in a higher transcriptional activity, indicating that the CE-LPH1 site contains other binding site(s) in addition to the Cdx-2-binding site.

Full Text

The Full Text of this article is available as a PDF (336K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Mantei N, Villa M, Enzler T, Wacker H, Boll W, James P, Hunziker W, Semenza G. Complete primary structure of human and rabbit lactase-phlorizin hydrolase: implications for biosynthesis, membrane anchoring and evolution of the enzyme. EMBO J. 1988 Sep;7(9):2705–2713. [PMC free article] [PubMed]
  • Rings EH, Büller HA, de Boer PA, Grand RJ, Montgomery RK, Lamers WH, Charles R, Moorman AF. Messenger RNA sorting in enterocytes. Co-localization with encoded proteins. FEBS Lett. 1992 Mar 30;300(2):183–187. [PubMed]
  • Freund JN, Torp N, Duluc I, Foltzer-Jourdainne C, Danielsen M, Raul F. Comparative expression of the mRNA for three intestinal hydrolases during postnatal development in the rat. Cell Mol Biol. 1990;36(6):729–736. [PubMed]
  • Rings EH, de Boer PA, Moorman AF, van Beers EH, Dekker J, Montgomery RK, Grand RJ, Büller HA. Lactase gene expression during early development of rat small intestine. Gastroenterology. 1992 Oct;103(4):1154–1161. [PubMed]
  • Maiuri L, Rossi M, Raia V, Garipoli V, Hughes LA, Swallow D, Norén O, Sjöström H, Auricchio S. Mosaic regulation of lactase in human adult-type hypolactasia. Gastroenterology. 1994 Jul;107(1):54–60. [PubMed]
  • Norén O, Dabelsteen E, Høyer PE, Olsen J, Sjöström H, Hansen GH. Onset of transcription of the aminopeptidase N (leukemia antigen CD 13) gene at the crypt/villus transition zone during rabbit enterocyte differentiation. FEBS Lett. 1989 Dec 18;259(1):107–112. [PubMed]
  • Traber PG, Yu L, Wu GD, Judge TA. Sucrase-isomaltase gene expression along crypt-villus axis of human small intestine is regulated at level of mRNA abundance. Am J Physiol. 1992 Jan;262(1 Pt 1):G123–G130. [PubMed]
  • Büller HA, Kothe MJ, Goldman DA, Grubman SA, Sasak WV, Matsudaira PT, Montgomery RK, Grand RJ. Coordinate expression of lactase-phlorizin hydrolase mRNA and enzyme levels in rat intestine during development. J Biol Chem. 1990 Apr 25;265(12):6978–6983. [PubMed]
  • Torp N, Rossi M, Troelsen JT, Olsen J, Danielsen EM. Lactase-phlorizin hydrolase and aminopeptidase N are differentially regulated in the small intestine of the pig. Biochem J. 1993 Oct 1;295(Pt 1):177–182. [PMC free article] [PubMed]
  • Keller P, Zwicker E, Mantei N, Semenza G. The levels of lactase and of sucrase-isomaltase along the rabbit small intestine are regulated both at the mRNA level and post-translationally. FEBS Lett. 1992 Nov 30;313(3):265–269. [PubMed]
  • Rings EH, Krasinski SD, van Beers EH, Moorman AF, Dekker J, Montgomery RK, Grand RJ, Büller HA. Restriction of lactase gene expression along the proximal-to-distal axis of rat small intestine occurs during postnatal development. Gastroenterology. 1994 May;106(5):1223–1232. [PubMed]
  • Montgomery RK, Büller HA, Rings EH, Grand RJ. Lactose intolerance and the genetic regulation of intestinal lactase-phlorizin hydrolase. FASEB J. 1991 Oct;5(13):2824–2832. [PubMed]
  • Lloyd M, Mevissen G, Fischer M, Olsen W, Goodspeed D, Genini M, Boll W, Semenza G, Mantei N. Regulation of intestinal lactase in adult hypolactasia. J Clin Invest. 1992 Feb;89(2):524–529. [PMC free article] [PubMed]
  • Escher JC, de Koning ND, van Engen CG, Arora S, Büller HA, Montgomery RK, Grand RJ. Molecular basis of lactase levels in adult humans. J Clin Invest. 1992 Feb;89(2):480–483. [PMC free article] [PubMed]
  • Lacey SW, Naim HY, Magness RR, Gething MJ, Sambrook JF. Expression of lactase-phlorizin hydrolase in sheep is regulated at the RNA level. Biochem J. 1994 Sep 15;302(Pt 3):929–935. [PMC free article] [PubMed]
  • Krasinski SD, Estrada G, Yeh KY, Yeh M, Traber PG, Rings EH, Büller HA, Verhave M, Montgomery RK, Grand RJ. Transcriptional regulation of intestinal hydrolase biosynthesis during postnatal development in rats. Am J Physiol. 1994 Oct;267(4 Pt 1):G584–G594. [PubMed]
  • Fajardo O, Naim HY, Lacey SW. The polymorphic expression of lactase in adults is regulated at the messenger RNA level. Gastroenterology. 1994 May;106(5):1233–1241. [PubMed]
  • Harvey CB, Wang Y, Hughes LA, Swallow DM, Thurrell WP, Sams VR, Barton R, Lanzon-Miller S, Sarner M. Studies on the expression of intestinal lactase in different individuals. Gut. 1995 Jan;36(1):28–33. [PMC free article] [PubMed]
  • Troelsen JT, Mehlum A, Olsen J, Spodsberg N, Hansen GH, Prydz H, Norén O, Sjöström H. 1 kb of the lactase-phlorizin hydrolase promoter directs post-weaning decline and small intestinal-specific expression in transgenic mice. FEBS Lett. 1994 Apr 11;342(3):291–296. [PubMed]
  • Troelsen JT, Olsen J, Norén O, Sjöström H. A novel intestinal trans-factor (NF-LPH1) interacts with the lactase-phlorizin hydrolase promoter and co-varies with the enzymatic activity. J Biol Chem. 1992 Oct 5;267(28):20407–20411. [PubMed]
  • Boukamel R, Freund JN. The cis-element CE-LPH1 of the rat intestinal lactase gene promoter interacts in vitro with several nuclear factors present in endodermal tissues. FEBS Lett. 1994 Oct 10;353(1):108–112. [PubMed]
  • Wu GD, Chen L, Forslund K, Traber PG. Hepatocyte nuclear factor-1 alpha (HNF-1 alpha) and HNF-1 beta regulate transcription via two elements in an intestine-specific promoter. J Biol Chem. 1994 Jun 24;269(25):17080–17085. [PubMed]
  • Markowitz AJ, Wu GD, Birkenmeier EH, Traber PG. The human sucrase-isomaltase gene directs complex patterns of gene expression in transgenic mice. Am J Physiol. 1993 Sep;265(3 Pt 1):G526–G539. [PubMed]
  • Traber PG, Wu GD, Wang W. Novel DNA-binding proteins regulate intestine-specific transcription of the sucrase-isomaltase gene. Mol Cell Biol. 1992 Aug;12(8):3614–3627. [PMC free article] [PubMed]
  • Wu GD, Wang W, Traber PG. Isolation and characterization of the human sucrase-isomaltase gene and demonstration of intestine-specific transcriptional elements. J Biol Chem. 1992 Apr 15;267(11):7863–7870. [PubMed]
  • Troelsen JT, Olsen J, Mitchelmore C, Hansen GH, Sjöström H, Norén O. Two intestinal specific nuclear factors binding to the lactase-phlorizin hydrolase and sucrase-isomaltase promoters are functionally related oligomeric molecules. FEBS Lett. 1994 Apr 11;342(3):297–301. [PubMed]
  • Suh E, Chen L, Taylor J, Traber PG. A homeodomain protein related to caudal regulates intestine-specific gene transcription. Mol Cell Biol. 1994 Nov;14(11):7340–7351. [PMC free article] [PubMed]
  • German MS, Wang J, Chadwick RB, Rutter WJ. Synergistic activation of the insulin gene by a LIM-homeo domain protein and a basic helix-loop-helix protein: building a functional insulin minienhancer complex. Genes Dev. 1992 Nov;6(11):2165–2176. [PubMed]
  • Jin T, Drucker DJ. Activation of proglucagon gene transcription through a novel promoter element by the caudal-related homeodomain protein cdx-2/3. Mol Cell Biol. 1996 Jan;16(1):19–28. [PMC free article] [PubMed]
  • Schöler HR, Hatzopoulos AK, Balling R, Suzuki N, Gruss P. A family of octamer-specific proteins present during mouse embryogenesis: evidence for germline-specific expression of an Oct factor. EMBO J. 1989 Sep;8(9):2543–2550. [PMC free article] [PubMed]
  • Olsen J, Laustsen L, Kärnström U, Sjöström H, Norén O. Tissue-specific interactions between nuclear proteins and the aminopeptidase N promoter. J Biol Chem. 1991 Sep 25;266(27):18089–18096. [PubMed]
  • Chantret I, Barbat A, Dussaulx E, Brattain MG, Zweibaum A. Epithelial polarity, villin expression, and enterocytic differentiation of cultured human colon carcinoma cells: a survey of twenty cell lines. Cancer Res. 1988 Apr 1;48(7):1936–1942. [PubMed]
  • Boll W, Wagner P, Mantei N. Structure of the chromosomal gene and cDNAs coding for lactase-phlorizin hydrolase in humans with adult-type hypolactasia or persistence of lactase. Am J Hum Genet. 1991 May;48(5):889–902. [PMC free article] [PubMed]
  • Villa M, Brunschwiler D, Gächter T, Boll W, Semenza G, Mantei N. Region-specific expression of multiple lactase-phlorizin hydrolase genes in intestine of rabbit. FEBS Lett. 1993 Dec 20;336(1):70–74. [PubMed]
  • Boukamel R, Freund JN. The rat LPH gene 5' region: comparative structure with the human gene. DNA Seq. 1992;3(2):119–121. [PubMed]
  • Verhave M, Krasinski SD, Maas SM, Smiers FJ, Mishra K, Breeuwsma NG, Naim HY, Grand RJ. Further characterization of the 5'-flanking region of the rat lactase-phlorizin hydrolase gene. Biochem Biophys Res Commun. 1995 Apr 26;209(3):989–995. [PubMed]
  • Markowitz AJ, Wu GD, Bader A, Cui Z, Chen L, Traber PG. Regulation of lineage-specific transcription of the sucrase-isomaltase gene in transgenic mice and cell lines. Am J Physiol. 1995 Dec;269(6 Pt 1):G925–G939. [PubMed]
  • James R, Kazenwadel J. Homeobox gene expression in the intestinal epithelium of adult mice. J Biol Chem. 1991 Feb 15;266(5):3246–3251. [PubMed]
  • James R, Erler T, Kazenwadel J. Structure of the murine homeobox gene cdx-2. Expression in embryonic and adult intestinal epithelium. J Biol Chem. 1994 May 27;269(21):15229–15237. [PubMed]
  • Drummond F, Sowden J, Morrison K, Edwards YH. The caudal-type homeobox protein Cdx-2 binds to the colon promoter of the carbonic anhydrase 1 gene. Eur J Biochem. 1996 Mar 1;236(2):670–681. [PubMed]
  • Suh E, Traber PG. An intestine-specific homeobox gene regulates proliferation and differentiation. Mol Cell Biol. 1996 Feb;16(2):619–625. [PMC free article] [PubMed]
  • Wang MM, Reed RR. Molecular cloning of the olfactory neuronal transcription factor Olf-1 by genetic selection in yeast. Nature. 1993 Jul 8;364(6433):121–126. [PubMed]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Gene
    Gene links
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence links
  • MedGen
    Related information in MedGen
  • Nucleotide
    Published Nucleotide sequences
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...