The murine Muc2 mucin gene is transcriptionally regulated by the zinc-finger GATA-4 transcription factor in intestinal cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Biochemical and Biophysical Research Communications Année : 2004

The murine Muc2 mucin gene is transcriptionally regulated by the zinc-finger GATA-4 transcription factor in intestinal cells

Résumé

MUC2, the major mucin in the intestine, is expressed early during development and shows an altered expression pattern in intestinal bowel diseases. However, the mechanisms responsible for MUC2 expression in the intestine during these events are largely unknown. Having found putative GATA binding sites in the murine Muc2 promoter and that GATA-4 is expressed in Muc2-expressing goblet cells of the mouse small intestine, we undertook to study its regulation by this transcription factor. A panel of deletion mutants made in pGL3 vector and covering 2.2 kb of the promoter were used to transfect the murine CMT-93 colorectal cancer cell line. The role of GATA-4 on Muc2 gene regulation was investigated by RT-PCR and co-transfections in the presence of expression vectors encoding either wild-type or mutated GATA-4 or by mutating the GATA-4 site identified within Muc2 promoter. Four GATA-4 cis-elements were identified in the promoter by EMSA and Muc2 promoter was efficiently activated when GATA-4 was overexpressed in the cells with a loss of transactivation when those sites were either mutated or a mutated form of GATA-4 was used. Altogether, these results identify Muc2, a goblet cell marker, as a new target gene of GATA-4 and point out an important role for this factor in Muc2 expression in the intestine. The mucus layer in the lumen of the gut forms a physical barrier against microorganisms and insoluble material [1]. Goblet cells are a hallmark of the intestinal epithelium, and are known to secrete mucins that participate in mucus formation to protect the underlying mucosa. The secretory mucin Muc2, a very large O-gly-coprotein, is particularly relevant for the study of goblet cell biology as it is exclusively and abundantly expressed by intestinal goblet cells [2,3]. It is produced throughout the gastro-intestinal tract increasing from small intestine to colon. Muc2 is expressed early during embryonic development of the intestine [4], which suggests that Muc2 transcription is under the influence of transcription factors responsible for intestinal development and cell differentiation. The early expression of mucin before mucus cell differentiation or during the process of differentiation indicates that they may be the targets of transcription factors responsible for those programs [5]. This hypothesis has been recently confirmed in a previous study
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hal-02905675 , version 1 (29-09-2020)

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Maria van Der Sluis, Monique H M Melis, Nicolas Jonckheere, Marie-Paule Ducourouble, Hans A Bü Ller A, et al.. The murine Muc2 mucin gene is transcriptionally regulated by the zinc-finger GATA-4 transcription factor in intestinal cells. Biochemical and Biophysical Research Communications, 2004, 325, pp.952 - 960. ⟨10.1016/j.bbrc.2004.10.108⟩. ⟨hal-02905675⟩

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