The mouse Muc3 mucin is a membrane-bound glycoprotein highly expressed in the intestinal tract. We have characterized the mouse Muc3 5′ structure and regulation of its promoter by cytokines and growth factors. The first two exons of Muc3 are separated by an intron of over 8 kb. Exon 3 contains the tandem repeat domain. Ten exons reside 3′ to the tandem repeat domain. The 5′ nonrepetitive sequence contains 104 amino acids characterized by a putative signal sequence, a single cysteine and 28% serine/threonine. No TATA box is found near the transcription start site. The promoter has consensus binding sites for AP1, CREB, SP1, NFκB, GATA binding protein and Cdx. Muc3 promoter constructs demonstrate that IL4, IL6, EGF or PMA increased promoter activity to 35-58% of control. TNFα and IFNγ showed lesser stimulation. These data indicate that cytokines and growth factors are capable of regulating Muc3 gene expression, suggesting that this protein may play an active role in intestinal mucosal defense.
|Original language||English (US)|
|Number of pages||11|
|Journal||Biochimica et Biophysica Acta - Gene Structure and Expression|
|State||Published - Jun 19 2003|
Bibliographical noteFunding Information:
This work was supported by a grant from the Crohn's and Colitis Foundation of America (LLS), a VA Merit Review Award (SBH) and the Research Service of the Veterans Affairs Medical Center, Minneapolis, MN.
- Gene regulation