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CEACAM1, a SOX9 direct transcriptional target identified in the colon epithelium

H Zalzali1, C Naudin, P Bastide

  • 1CNRS, UMR 5203, Institut de Génomique Fonctionnelle, Montpellier, France.

Oncogene
|September 17, 2008
PubMed

Insights

SOX9 is crucial for colon health, regulating CEACAM1 expression. This study identifies CEACAM1 as the first direct SOX9 target in the colon epithelium, impacting cell growth and tumor suppression.

Area of Science:

  • Molecular Biology
  • Genetics
  • Gastroenterology

Background:

  • SOX9 (SRY-box transcription factor 9) plays a role in intestinal development.
  • The direct transcriptional targets of SOX9 in the colon epithelium remain largely unknown.
  • SOX9 gene deletion impacts colon epithelium morphology and causes hyperplasia.

Purpose of the Study:

  • To identify direct transcriptional targets of SOX9 in the colon epithelium.
  • To investigate the role of SOX9 in regulating CEACAM1 expression.
  • To elucidate the mechanism of SOX9-mediated CEACAM1 transcriptional activation.

Main Methods:

  • Microarray analysis to identify potential SOX9 targets.
  • In vitro studies using human colonic cells to confirm SOX9-mediated CEACAM1 upregulation.
  • Analysis of SOX9-deficient mouse colon for CEACAM1 expression levels.
  • Promoter analysis, electrophoretic mobility shift assays (EMSA), and chromatin immunoprecipitation (ChIP) to confirm SOX9 binding to the CEACAM1 promoter.
  • Co-transfection assays to assess the role of p300 as a SOX9 co-activator.

Main Results:

  • Microarray analysis identified carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) as a potential SOX9 target.
  • SOX9 was demonstrated to upregulate CEACAM1 expression in human colonic cells.
  • CEACAM1 expression was reduced in SOX9-deficient mouse colon.
  • SOX9-binding sequences were identified in the CEACAM1 promoters of humans and rats.
  • EMSA and ChIP confirmed SOX9 binding to the human CEACAM1 promoter.
  • Histone acyl-transferase p300 acts as a SOX9 co-activator for CEACAM1 promoter activity.

Conclusions:

  • CEACAM1 is identified as the first direct transcriptional target of SOX9 in the colon epithelium.
  • SOX9 plays a significant role in the transcriptional activation of CEACAM1 in the colon.
  • These findings provide insights into the molecular mechanisms underlying SOX9 function in colon epithelial homeostasis and potentially in colorectal cancer development.

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