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Mucin 2 (MUC2) promoter characterization: an overview

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Abstract

Transgenic livestock have been studied with a well-known interest in improving quantitative and qualitative traits. In order to direct heterologous gene expression, it is indispensable to identify and characterize a promoter suitable for directing the expression of the gene of interest (GOI) in a tissue-specific way. The gastrointestinal tract is a desirable target for gene expression in several mammalian models. Throughout the surface of the intestinal epithelium, there is an intricate polymer network, formed by gel-forming mucins (especially MUC2 and MUC5AC, of which MUC2 is the major one), which plays a protective role due to the formation of a physical, chemical and immunological barrier between the organism and the environment. The characterization of the gel-forming mucins is difficult because of their large size and repetitive DNA sequences and domains. The main mucin in the small and large intestine, mucin 2 (MUC2), is expressed specifically in goblet cells. MUC2 plays an important role in intestinal homeostasis and its disruption is associated with several diseases and carcinomas. This mucin is also an important marker for elucidating mechanisms that regulate differentiation of the secretory cell lineage. This review presents the state of the art of MUC2 promoter structure and functional characterization.

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References

  • Akazawa C, Ishibashi M, Shimizu C, Nakanishi S, Kageyama R (1995) A mammalian helix-loop-helix factor structurally related to the product of Drosophila proneural gene atonal is a positive transcriptional regulator expressed in the developing nervous system. J Biol Chem 270:8730–8738

    CAS  PubMed  Google Scholar 

  • Almeida R, Silva E, Santos-Silva F, Silberg DG, Wang J, De Bolos C, David L (2003) Expression of intestine-specific transcription factors, CDX1 and CDX2, in intestinal metaplasia and gastric carcinomas. J Pathol 199:36–40

    PubMed  Google Scholar 

  • Ambort D, Johansson ME, Gustafsson JK, Nilsson HE, Ermund A, Johansson BR, Koeck PJ, Hebert H, Hansson GC (2012) Calcium and pH-dependent packing and release of the gel-forming MUC2 mucin. Proc Natl Acad Sci U S A 109:5645–5650

    CAS  PubMed  PubMed Central  Google Scholar 

  • Artis D, Grencis RK (2008) The intestinal epithelium: sensors to effectors in nematode infection. Mucosal Immunol 1:252–264

    CAS  PubMed  Google Scholar 

  • Aslam F, Palumbo L, Augenlicht LH, Velcich A (2001) The Sp family of transcription factors in the regulation of the human and mouse MUC2 gene promoters. Cancer Res 61:570–576

    CAS  PubMed  Google Scholar 

  • Audie JP, Janin A, Porchet N, Copin MC, Gosselin B, Aubert JP (1993) Expression of human mucin genes in respiratory, digestive, and reproductive tracts ascertained by in situ hybridization. J Histochem Cytochem 41:1479–1485

    CAS  PubMed  Google Scholar 

  • Backstrom M, Ambort D, Thomsson E, Johansson ME, Hansson GC (2013) Increased understanding of the biochemistry and biosynthesis of MUC2 and other gel-forming mucins through the recombinant expression of their protein domains. Mol Biotechnol 54:250–256

    PubMed  PubMed Central  Google Scholar 

  • Bara J, Forgue-Lafitte ME, Maurin N, Flejou JF, Zimber A (2003) Abnormal expression of gastric mucin in human and rat aberrant crypt foci during colon carcinogenesis. Tumour Biol 24:109–115

    CAS  PubMed  Google Scholar 

  • Bertolini LR, Meade H, Lazzarotto CR, Martins LT, Tavares KC, Bertolini M, Murray JD (2016) The transgenic animal platform for biopharmaceutical production. Transgenic Res 25:329–343

    CAS  PubMed  Google Scholar 

  • Birchenough GM, Johansson ME, Gustafsson JK, Bergstrom JH, Hansson GC (2015) New developments in goblet cell mucus secretion and function. Mucosal Immunol 8:712–719

    CAS  PubMed  PubMed Central  Google Scholar 

  • Birchenough GM, Nystrom EE, Johansson ME, Hansson GC (2016) A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion. Science 352:1535–1542

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bonser LR, Erle DJ (2017) Airway mucus and asthma: the role of MUC5AC and MUC5B. J Clin Med 6.

  • Boyle AP, Song L, Lee BK, London D, Keefe D, Birney E, Iyer VR, Crawford GE, Furey TS (2011) High-resolution genome-wide in vivo footprinting of diverse transcription factors in human cells. Genome Res 21:456–464

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bravo JC, Correa P (1999) Sulphomucins favour adhesion of Helicobacter pylori to metaplastic gastric mucosa. J Clin Pathol 52:137–140

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bu XD, Li N, Tian XQ, Huang PL (2011) Caco-2 and LS174T cell lines provide different models for studying mucin expression in colon cancer. Tissue Cell 43:201–206

    CAS  PubMed  Google Scholar 

  • Buisine MP, Devisme L, Savidge TC, Gespach C, Gosselin B, Porchet N, Aubert JP (1998) Mucin gene expression in human embryonic and fetal intestine. Gut 43:519–524

    CAS  PubMed  PubMed Central  Google Scholar 

  • Burger-van Paassen N, Vincent A, Puiman PJ, van der Sluis M, Bouma J, Boehm G, van Goudoever JB, van Seuningen I, Renes IB (2009) The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: implications for epithelial protection. Biochem J 420:211–219

    CAS  PubMed  Google Scholar 

  • Chang SK, Dohrman AF, Basbaum CB, Ho SB, Tsuda T, Toribara NW, Gum JR, Kim YS (1994) Localization of mucin (MUC2 and MUC3) messenger RNA and peptide expression in human normal intestine and colon cancer. Gastroenterology 107:28–36

    CAS  PubMed  Google Scholar 

  • Chen Y, Zhao YH, Kalaslavadi TB, Hamati E, Nehrke K, Le AD, Ann DK, Wu R (2004) Genome-wide search and identification of a novel gel-forming mucin MUC19/Muc19 in glandular tissues. Am J Respir Cell Mol Biol 30:155–165

    CAS  PubMed  Google Scholar 

  • Cliffe LJ, Grencis RK (2004) The Trichuris muris system: a paradigm of resistance and susceptibility to intestinal nematode infection. Adv Parasitol 57:255–307

    PubMed  Google Scholar 

  • Corfield AP (2015) Mucins: a biologically relevant glycan barrier in mucosal protection. Biochim Biophys Acta 1850:236–252

    CAS  Google Scholar 

  • Correa P (1988) A human model of gastric carcinogenesis. Cancer Res 48:3554–3560

    CAS  PubMed  Google Scholar 

  • Craanen ME, Blok P, Dekker W, Ferwerda J, Tytgat GN (1992) Subtypes of intestinal metaplasia and Helicobacter pylori. Gut 33:597–600

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cuddapah S, Jothi R, Schones DE, Roh TY, Cui K, Zhao K (2009) Global analysis of the insulator binding protein CTCF in chromatin barrier regions reveals demarcation of active and repressive domains. Genome Res 19:24–32

    CAS  PubMed  PubMed Central  Google Scholar 

  • de Bustros A, Nelkin BD, Silverman A, Ehrlich G, Poiesz B, Baylin SB (1988) The short arm of chromosome 11 is a “hot spot” for hypermethylation in human neoplasia. Proc Natl Acad Sci U S A 85:5693–5697

    PubMed  PubMed Central  Google Scholar 

  • Demouveaux B, Gouyer V, Gottrand F, Narita T, Desseyn JL (2018) Gel-forming mucin interactome drives mucus viscoelasticity. Adv Colloid Interf Sci 252:69–82

    CAS  Google Scholar 

  • Desseyn JL, Aubert JP, Porchet N, Laine A (2000) Evolution of the large secreted gel-forming mucins. Mol Biol Evol 17:1175–1184

    CAS  PubMed  Google Scholar 

  • Desseyn JL, Laine A (2003) Characterization of mouse muc6 and evidence of conservation of the gel-forming mucin gene cluster between human and mouse. Genomics 81:433–436

    CAS  PubMed  Google Scholar 

  • Desseyn JL, Tetaert D, Gouyer V (2008) Architecture of the large membrane-bound mucins. Gene 410:215–222

    CAS  PubMed  Google Scholar 

  • DeVack C, Lupp B, Nichols M, Kowenz-Leutz E, Schmid W, Schutz G (1993) Characterization of the nuclear proteins binding the CACCC element of a glucocorticoid-responsive enhancer in the tyrosine aminotransferase gene. Eur J Biochem 211:459–465

    CAS  PubMed  Google Scholar 

  • Dittmer J, Gegonne A, Gitlin SD, Ghysdael J, Brady JN (1994) Regulation of parathyroid hormone-related protein (PTHrP) gene expression. Sp1 binds through an inverted CACCC motif and regulates promoter activity in cooperation with Ets1. J Biol Chem 269:21428–21434

    CAS  PubMed  Google Scholar 

  • Ferreira B, Marcos NT, David L, Nakayama J, Reis CA (2006) Terminal alpha1,4-linked N-acetylglucosamine in Helicobacter pylori-associated intestinal metaplasia of the human stomach and gastric carcinoma cell lines. J Histochem Cytochem 54:585–591

    CAS  PubMed  Google Scholar 

  • Filipe MI, Munoz N, Matko I, Kato I, Pompe-Kirn V, Jutersek A, Teuchmann S, Benz M, Prijon T (1994) Intestinal metaplasia types and the risk of gastric cancer: a cohort study in Slovenia. Int J Cancer 57:324–329

    CAS  PubMed  Google Scholar 

  • Forgue-Lafitte ME, Fabiani B, Levy PP, Maurin N, Flejou JF, Bara J (2007) Abnormal expression of M1/MUC5AC mucin in distal colon of patients with diverticulitis, ulcerative colitis and cancer. Int J Cancer 121:1543–1549

    CAS  PubMed  Google Scholar 

  • Fraiture MA, Herman P, Taverniers I, De Loose M, Deforce D, Roosens NH (2015) Current and new approaches in GMO detection: challenges and solutions. Biomed Res Int 2015:392872

    PubMed  PubMed Central  Google Scholar 

  • Fridge JL, Conrad C, Gerson L, Castillo RO, Cox K (2007) Risk factors for small bowel bacterial overgrowth in cystic fibrosis. J Pediatr Gastroenterol Nutr 44:212–218

    PubMed  Google Scholar 

  • Gao N, White P, Kaestner KH (2009) Establishment of intestinal identity and epithelial-mesenchymal signaling by Cdx2. Dev Cell 16:588–599

    CAS  PubMed  PubMed Central  Google Scholar 

  • Genta RM, Gurer IE, Graham DY, Krishnan B, Segura AM, Gutierrez O, Kim JG, Burchette JL,J (1996) Adherence of Helicobacter pylori to areas of incomplete intestinal metaplasia in the gastric mucosa. Gastroenterology 111:1206–1211

    CAS  PubMed  Google Scholar 

  • Girling A, Bartkova J, Burchell J, Gendler S, Gillett C, Taylor-Papadimitriou J (1989) A core protein epitope of the polymorphic epithelial mucin detected by the monoclonal antibody SM-3 is selectively exposed in a range of primary carcinomas. Int J Cancer 43:1072–1076

    CAS  PubMed  Google Scholar 

  • Gosalia N, Leir SH, Harris A (2013) Coordinate regulation of the gel-forming mucin genes at chromosome 11p15.5. J Biol Chem 288:6717–6725

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gouyer V, Dubuquoy L, Robbe-Masselot C, Neut C, Singer E, Plet S, Geboes K, Desreumaux P, Gottrand F, Desseyn JL (2015) Delivery of a mucin domain enriched in cysteine residues strengthens the intestinal mucous barrier. Sci Rep 5:9577

    CAS  PubMed  PubMed Central  Google Scholar 

  • Griffiths B, Matthews DJ, West L, Attwood J, Povey S, Swallow DM, Gum JR, Kim YS (1990) Assignment of the polymorphic intestinal mucin gene (MUC2) to chromosome 11p15. Ann Hum Genet 54:277–285

    CAS  PubMed  Google Scholar 

  • Gum JR, Hicks JW, Kim YS (1997) Identification and characterization of the MUC2 (human intestinal mucin) gene 5′-flanking region: promoter activity in cultured cells. Biochem J 325(Pt 1):259–267

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gum JR Jr, Hicks JW, Gillespie AM, Carlson EJ, Komuves L, Karnik S, Hong JC, Epstein CJ, Kim YS (1999) Goblet cell-specific expression mediated by the MUC2 mucin gene promoter in the intestine of transgenic mice. Am J Phys 276:G666–G676

    CAS  Google Scholar 

  • Gum JR Jr, Hicks JW, Toribara NW, Siddiki B, Kim YS (1994) Molecular cloning of human intestinal mucin (MUC2) cDNA. Identification of the amino terminus and overall sequence similarity to prepro-von Willebrand factor. J Biol Chem 269:2440–2446

    CAS  PubMed  Google Scholar 

  • Hagen G, Muller S, Beato M, Suske G (1992) Cloning by recognition site screening of two novel GT box binding proteins: a family of Sp1 related genes. Nucleic Acids Res 20:5519–5525

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hakomori S (1989) Aberrant glycosylation in tumors and tumor-associated carbohydrate antigens. Adv Cancer Res 52:257–331

    CAS  PubMed  Google Scholar 

  • Hasnain SZ, Evans CM, Roy M, Gallagher AL, Kindrachuk KN, Barron L, Dickey BF, Wilson MS, Wynn TA, Grencis RK, Thornton DJ (2011) Muc5ac: a critical component mediating the rejection of enteric nematodes. J Exp Med 208:893–900

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hasnain SZ, Wang H, Ghia JE, Haq N, Deng Y, Velcich A, Grencis RK, Thornton DJ, Khan WI (2010) Mucin gene deficiency in mice impairs host resistance to an enteric parasitic infection. Gastroenterology 138:1763–1771

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hatayama H, Iwashita J, Kuwajima A, Abe T (2007) The short chain fatty acid, butyrate, stimulates MUC2 mucin production in the human colon cancer cell line, LS174T. Biochem Biophys Res Commun 356:599–603

    CAS  PubMed  Google Scholar 

  • Ho SB, Niehans GA, Lyftogt C, Yan PS, Cherwitz DL, Gum ET, Dahiya R, Kim YS (1993) Heterogeneity of mucin gene expression in normal and neoplastic tissues. Cancer Res 53:641–651

    CAS  PubMed  Google Scholar 

  • Hoorens PR, Rinaldi M, Li RW, Goddeeris B, Claerebout E, Vercruysse J, Geldhof P (2011) Genome wide analysis of the bovine mucin genes and their gastrointestinal transcription profile. BMC Genomics 12:140

    CAS  PubMed  PubMed Central  Google Scholar 

  • Inatomi T, Spurr-Michaud S, Tisdale AS, Zhan Q, Feldman ST, Gipson IK (1996) Expression of secretory mucin genes by human conjunctival epithelia. Invest Ophthalmol Vis Sci 37:1684–1692

    CAS  PubMed  Google Scholar 

  • Johansson ME, Larsson JM, Hansson GC (2011) The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions. Proc Natl Acad Sci U S A 108(Suppl 1):4659–4665

    CAS  PubMed  Google Scholar 

  • Johansson ME, Phillipson M, Petersson J, Velcich A, Holm L, Hansson GC (2008) The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci U S A 105:15064–15069

    CAS  PubMed  PubMed Central  Google Scholar 

  • Johansson ME, Sjovall H, Hansson GC (2013) The gastrointestinal mucus system in health and disease. Nat Rev Gastroenterol Hepatol 10:352–361

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kawakubo M, Ito Y, Okimura Y, Kobayashi M, Sakura K, Kasama S, Fukuda MN, Fukuda M, Katsuyama T, Nakayama J (2004) Natural antibiotic function of a human gastric mucin against Helicobacter pylori infection. Science 305:1003–1006

    CAS  PubMed  Google Scholar 

  • Kim TH, Abdullaev ZK, Smith AD, Ching KA, Loukinov DI, Green RD, Zhang MQ, Lobanenkov VV, Ren B (2007) Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome. Cell 128:1231–1245

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lang T, Hansson GC, Samuelsson T (2007) Gel-forming mucins appeared early in metazoan evolution. Proc Natl Acad Sci U S A 104:16209–16214

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lang T, Klasson S, Larsson E, Johansson ME, Hansson GC, Samuelsson T (2016) Searching the evolutionary origin of epithelial mucus protein components-mucins and FCGBP. Mol Biol Evol 33:1921–1936

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lee K, Villena JA, Moon YS, Kim KH, Lee S, Kang C, Sul HS (2003) Inhibition of adipogenesis and development of glucose intolerance by soluble preadipocyte factor-1 (Pref-1). J Clin Invest 111:453–461

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lidell ME, Moncada DM, Chadee K, Hansson GC (2006) Entamoeba histolytica cysteine proteases cleave the MUC2 mucin in its C-terminal domain and dissolve the protective colonic mucus gel. Proc Natl Acad Sci U S A 103:9298–9303

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ma J, Rubin BK, Voynow JA (2017) Mucins, mucus, and goblet cells. Chest S0012-3692(17):33080–33085

    Google Scholar 

  • Matsukura N, Suzuki K, Kawachi T, Aoyagi M, Sugimura T, Kitaoka H, Numajiri H, Shirota A, Itabashi M, Hirota T (1980) Distribution of marker enzymes and mucin in intestinal metaplasia in human stomach and relation to complete and incomplete types of intestinal metaplasia to minute gastric carcinomas. J Natl Cancer Inst 65:231–240

    CAS  PubMed  Google Scholar 

  • Matsuoka Y, Pascall JC, Brown KD (1999) Quantitative analysis reveals differential expression of mucin (MUC2) and intestinal trefoil factor mRNAs along the longitudinal axis of rat intestine. Biochim Biophys Acta 1489:336–344

    CAS  PubMed  Google Scholar 

  • Maynard CL, Elson CO, Hatton RD, Weaver CT (2012) Reciprocal interactions of the intestinal microbiota and immune system. Nature 489:231–241

    CAS  PubMed  PubMed Central  Google Scholar 

  • Melo EO, Canavessi AM, Franco MM, Rumpf R (2007) Animal transgenesis: state of the art and applications. J Appl Genet 48:47–61

    PubMed  Google Scholar 

  • Merlo GR, Siddiqui J, Cropp CS, Liscia DS, Lidereau R, Callahan R, Kufe DW (1989) Frequent alteration of the DF3 tumor-associated antigen gene in primary human breast carcinomas. Cancer Res 49:6966–6971

    CAS  PubMed  Google Scholar 

  • Mesquita P, Jonckheere N, Almeida R, Ducourouble MP, Serpa J, Silva E, Pigny P, Silva FS, Reis C, Silberg D, Van Seuningen I, David L (2003) Human MUC2 mucin gene is transcriptionally regulated by cdx homeodomain proteins in gastrointestinal carcinoma cell lines. J Biol Chem 278:51549–51556

    CAS  PubMed  Google Scholar 

  • Mikhaylichenko O, Bondarenko V, Harnett D, Schor IE, Males M, Viales RR, Furlong EEM (2018) The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription. Genes Dev 32:42–57

    CAS  PubMed  PubMed Central  Google Scholar 

  • Moniaux N, Escande F, Porchet N, Aubert JP, Batra SK (2001) Structural organization and classification of the human mucin genes. Front Biosci 6:D1192–D1206

    CAS  PubMed  Google Scholar 

  • Nogami H, Ohmori H, Li JD, Gallup M, Gum J, Kim Y, Basbaum C (1997) Sp1 protein contributes to airway-specific rat MUC 2 mucin gene transcription. Gene 198:191–201

    CAS  PubMed  Google Scholar 

  • Ookawa K, Kudo T, Aizawa S, Saito H, Tsuchida S (2002) Transcriptional activation of the MUC2 gene by p53. J Biol Chem 277:48270–48275

    CAS  PubMed  Google Scholar 

  • Park ET, Oh HK, Gum JR Jr, Crawley SC, Kakar S, Engel J, Leow CC, Gao WQ, Kim YS (2006) HATH1 expression in mucinous cancers of the colorectum and related lesions. Clin Cancer Res 12:5403–5410

    CAS  PubMed  Google Scholar 

  • Perez-Sanchez J, Estensoro I, Redondo MJ, Calduch-Giner JA, Kaushik S, Sitja-Bobadilla A (2013) Mucins as diagnostic and prognostic biomarkers in a fish-parasite model: transcriptional and functional analysis. PLoS One 8:e65457

    CAS  PubMed  PubMed Central  Google Scholar 

  • Perez-Vilar J, Hill RL (1999) The structure and assembly of secreted mucins. J Biol Chem 274:31751–31754

    CAS  PubMed  Google Scholar 

  • Phillips JE, Corces VG (2009) CTCF: master weaver of the genome. Cell 137:1194–1211

    PubMed  PubMed Central  Google Scholar 

  • Pigny P, Guyonnet-Duperat V, Hill AS, Pratt WS, Galiegue-Zouitina S, d'Hooge MC, Laine A, Van-Seuningen I, Degand P, Gum JR, Kim YS, Swallow DM, Aubert JP, Porchet N (1996) Human mucin genes assigned to 11p15.5: identification and organization of a cluster of genes. Genomics 38:340–352

    CAS  PubMed  Google Scholar 

  • Pinto-de-Sousa J, David L, Reis CA, Gomes R, Silva L, Pimenta A (2002) Mucins MUC1, MUC2, MUC5AC and MUC6 expression in the evaluation of differentiation and clinico-biological behaviour of gastric carcinoma. Virchows Arch 440:304–310

    CAS  PubMed  Google Scholar 

  • Rana SS, Chandrasekaran EV, Mendicino J (1987) Structures of the sialylated oligosaccharide chains in swine tracheal mucin glycoproteins. J Biol Chem 262:3654–3659

    CAS  PubMed  Google Scholar 

  • Reis CA, David L, Carvalho F, Mandel U, de Bolos C, Mirgorodskaya E, Clausen H, Sobrinho-Simoes M (2000) Immunohistochemical study of the expression of MUC6 mucin and co-expression of other secreted mucins (MUC5AC and MUC2) in human gastric carcinomas. J Histochem Cytochem 48:377–388

    CAS  PubMed  Google Scholar 

  • Reis CA, David L, Correa P, Carneiro F, de Bolos C, Garcia E, Mandel U, Clausen H, Sobrinho-Simoes M (1999) Intestinal metaplasia of human stomach displays distinct patterns of mucin (MUC1, MUC2, MUC5AC, and MUC6) expression. Cancer Res 59:1003–1007

    CAS  PubMed  Google Scholar 

  • Ren CY, Akiyama Y, Miyake S, Yuasa Y (2004) Transcription factor GATA-5 selectively up-regulates mucin gene expression. J Cancer Res Clin Oncol 130:245–252

    CAS  PubMed  Google Scholar 

  • Ridley C, Kouvatsos N, Raynal BD, Howard M, Collins RF, Desseyn JL, Jowitt TA, Baldock C, Davis CW, Hardingham TE, Thornton DJ (2014) Assembly of the respiratory mucin MUC5B: a new model for a gel-forming mucin. J Biol Chem 289:16409–16420

    CAS  PubMed  PubMed Central  Google Scholar 

  • Robbe C, Capon C, Maes E, Rousset M, Zweibaum A, Zanetta JP, Michalski JC (2003) Evidence of regio-specific glycosylation in human intestinal mucins: presence of an acidic gradient along the intestinal tract. J Biol Chem 278:46337–46348

    CAS  PubMed  Google Scholar 

  • Rodriguez-Pineiro AM, Bergstrom JH, Ermund A, Gustafsson JK, Schutte A, Johansson ME, Hansson GC (2013) Studies of mucus in mouse stomach, small intestine, and colon. II. Gastrointestinal mucus proteome reveals Muc2 and Muc5ac accompanied by a set of core proteins. Am J Physiol Gastrointest Liver Physiol 305:G348–G356

    CAS  PubMed  PubMed Central  Google Scholar 

  • Roy MG, Livraghi-Butrico A, Fletcher AA, McElwee MM, Evans SE, Boerner RM, Alexander SN, Bellinghausen LK, Song AS, Petrova YM, Tuvim MJ, Adachi R, Romo I, Bordt AS, Bowden MG, Sisson JH, Woodruff PG, Thornton DJ, Rousseau K, De la Garza MM, Moghaddam SJ, Karmouty-Quintana H, Blackburn MR, Drouin SM, Davis CW, Terrell KA, Grubb BR, O’Neal WK, Flores SC, Cota-Gomez A, Lozupone CA, Donnelly JM, Watson AM, Hennessy CE, Keith RC, Yang IV, Barthel L, Henson PM, Janssen WJ, Schwartz DA, Boucher RC, Dickey BF, Evans CM (2014) Muc5b is required for airway defence. Nature 505:412–416

    CAS  PubMed  Google Scholar 

  • Sadasivan VD, Narpala SR, Budil DE, Sacco A Jr, Carrier RL (2011) Modeling the human intestinal mucin (MUC2) C-terminal cystine knot dimer. J Mol Model 17:2953–2963

    CAS  PubMed  Google Scholar 

  • Springer GF, Desai PR, Ghazizadeh M, Tegtmeyer H (1995) T/Tn pancarcinoma autoantigens: fundamental, diagnostic, and prognostic aspects. Cancer Detect Prev 19:173–182

    CAS  PubMed  Google Scholar 

  • Stoltz DA, Rokhlina T, Ernst SE, Pezzulo AA, Ostedgaard LS, Karp PH, Samuel MS, Reznikov LR, Rector MV, Gansemer ND, Bouzek DC, Abou Alaiwa MH, Hoegger MJ, Ludwig PS, Taft PJ, Wallen TJ, Wohlford-Lenane C, McMenimen JD, Chen JH, Bogan KL, Adam RJ, Hornick EE, GAt N, Hoffman EA, Chang EH, Zabner J, Mc Cray PB Jr, Prather RS, Meyerholz DK, Welsh MJ (2013) Intestinal CFTR expression alleviates meconium ileus in cystic fibrosis pigs. J Clin Invest 123:2685–2693

    CAS  PubMed  PubMed Central  Google Scholar 

  • Strous GJ, Dekker J (1992) Mucin-type glycoproteins. Crit Rev Biochem Mol Biol 27:57–92

    CAS  PubMed  Google Scholar 

  • Sweetser DA, Hauft SM, Hoppe PC, Birkenmeier EH, Gordon JI (1988) Transgenic mice containing intestinal fatty acid-binding protein-human growth hormone fusion genes exhibit correct regional and cell-specific expression of the reporter gene in their small intestine. Proc Natl Acad Sci U S A 85:9611–9615

    CAS  PubMed  PubMed Central  Google Scholar 

  • Teixeira A, David L, Reis CA, Costa J, Sobrinho-Simoes M (2002) Expression of mucins (MUC1, MUC2, MUC5AC, and MUC6) and type 1 Lewis antigens in cases with and without Helicobacter pylori colonization in metaplastic glands of the human stomach. J Pathol 197:37–43

    PubMed  Google Scholar 

  • Thornton DJ, Rousseau K, McGuckin MA (2008) Structure and function of the polymeric mucins in airways mucus. Annu Rev Physiol 70:459–486

    CAS  PubMed  Google Scholar 

  • van der Post S, Thomsson KA, Hansson GC (2014) Multiple enzyme approach for the characterization of glycan modifications on the C-terminus of the intestinal MUC2 mucin. J Proteome Res 13:6013–6023

    PubMed  PubMed Central  Google Scholar 

  • Van der Sluis M, De Koning BA, De Bruijn AC, Velcich A, Meijerink JP, Van Goudoever JB, Buller HA, Dekker J, Van Seuningen I, Renes IB, Einerhand AW (2006) Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 131:117–129

    PubMed  Google Scholar 

  • van der Sluis M, Melis MH, Jonckheere N, Ducourouble MP, Buller HA, Renes I, Einerhand AW, Van Seuningen I (2004) The murine Muc2 mucin gene is transcriptionally regulated by the zinc-finger GATA-4 transcription factor in intestinal cells. Biochem Biophys Res Commun 325:952–960

    PubMed  Google Scholar 

  • van der Sluis M, Vincent A, Bouma J, Korteland-Van Male A, van Goudoever JB, Renes IB, Van Seuningen I (2008) Forkhead box transcription factors Foxa1 and Foxa2 are important regulators of Muc2 mucin expression in intestinal epithelial cells. Biochem Biophys Res Commun 369:1108–1113

    PubMed  Google Scholar 

  • Velcich A, Palumbo L, Selleri L, Evans G, Augenlicht L (1997) Organization and regulatory aspects of the human intestinal mucin gene (MUC2) locus. J Biol Chem 272:7968–7976

    CAS  PubMed  Google Scholar 

  • Velcich A, Yang W, Heyer J, Fragale A, Nicholas C, Viani S, Kucherlapati R, Lipkin M, Yang K, Augenlicht L (2002) Colorectal cancer in mice genetically deficient in the mucin Muc2. Science 295:1726–1729

    CAS  PubMed  Google Scholar 

  • Verdugo P (2012) Supramolecular dynamics of mucus. Cold Spring Harb Perspect Med 2

  • Vincent A, Perrais M, Desseyn JL, Aubert JP, Pigny P, Van Seuningen I (2007) Epigenetic regulation (DNA methylation, histone modifications) of the 11p15 mucin genes (MUC2, MUC5AC, MUC5B, MUC6) in epithelial cancer cells. Oncogene 26:6566–6576

    CAS  PubMed  Google Scholar 

  • Wang Y, Lee K, Moon YS, Ahmadian M, Kim KH, Roder K, Kang C, Sul HS (2015) Overexpression of Pref-1 in pancreatic islet beta-cells in mice causes hyperinsulinemia with increased islet mass and insulin secretion. Biochem Biophys Res Commun 461:630–635

    CAS  PubMed  PubMed Central  Google Scholar 

  • Woodfint RM, Chen PR, Ahn J, Suh Y, Hwang S, Lee SS, Lee K (2017) Identification of the MUC2 promoter as a strong promoter for intestinal gene expression through generation of transgenic quail expressing GFP in gut epithelial cells. Int J Mol Sci 18(1):196

    PubMed Central  Google Scholar 

  • Zawel L, Reinberg D (1995) Common themes in assembly and function of eukaryotic transcription complexes. Annu Rev Biochem 64:533–561

    CAS  PubMed  Google Scholar 

  • Zhu L, Lee P, Yu D, Tao S, Chen Y (2011) Cloning and characterization of human MUC19 gene. Am J Respir Cell Mol Biol 45:348–358

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Federal University of Tocantins (UFT), Rua Bandejós, chácaras 69/72, Zona Rural, Gurupi, TO, 77402-970, Brazil

    Melissa Shizue de A. Yamashita

  2. EMBRAPA Genetic Resources and Biotechnology, PqEB Av W5 Norte, Brasilia, DF, 70770-917, Brazil

    Eduardo O. Melo

Authors
  1. Melissa Shizue de A. Yamashita
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  2. Eduardo O. Melo
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Correspondence to Melissa Shizue de A. Yamashita.

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Yamashita, M.S.d.A., Melo, E.O. Mucin 2 (MUC2) promoter characterization: an overview. Cell Tissue Res 374, 455–463 (2018). https://doi.org/10.1007/s00441-018-2916-9

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  • DOI: https://doi.org/10.1007/s00441-018-2916-9

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