Characterization of the mouse Muc3 membrane bound intestinal mucin 5' coding and promoter regions: regulation by inflammatory cytokines.
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, NF kappa B, GATA binding protein and Cdx. Muc3 promoter constructs demonstrate that IL4, IL6, EGF or PMA increased promoter activity to 35-58% of control. TNF alpha and IFN gamma 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.
Shekels
Laurie L
LL
Department of Medicine, University of Minnesota and VA Medical Center, Research 151, 1 Veterans Drive, Minneapolis, MN 55417, USA. chaurie@scottdata.com
Ho
Samuel B
SB
D024506:5' Flanking Region; D020121:5' Untranslated Regions; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D005091:Exons; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D055263:Mucin-3; D009077:Mucins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020080:Tandem Repeat Sequences; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation
D020121:5' Untranslated Regions; D016207:Cytokines; D006133:Growth Substances; C524641:Muc3 protein, mouse; D055263:Mucin-3; D009077:Mucins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma