1,4-Galactosyltransferase (4-GT) is a constitutively expressed enzyme that synthesizes the 4-N-acetyllactosamine structure in glycoconjugates. In mammals, 4-GT has been recruited for a second biosynthetic function, the production of lactose which occurs exclusively in the lactating mammary gland. In somatic tissues, the murine 4-GT gene specifies two mRNAs of 4.1 and 3.9 kilobases (kb), as a consequence of initiation at two different start sites 200 base pairs apart. We have proposed that the region upstream of the 4.1-kb start site functions as a housekeeping promoter, while the region adjacent to the 3.9-kb start site functions primarily as a mammary gland-specific promoter (Harduin-Lepers, A., Shaper, J. H., and Shaper, N. L.(1993) J. Biol. Chem. 268, 14348-14359).

Using DNase I footprinting and electrophoretic mobility shift assays, we show that the region immediately upstream of the 4.1-kb start site is occupied mainly by the ubiquitous factor Sp1. In contrast, the region adjacent to the 3.9-kb start site is bound by multiple proteins which include the tissue-restricted factor AP2, a mammary gland-specific form of CTF/NF1, Sp1, as well as a candidate negative regulatory factor that represses transcription from the 3.9-kb start site. These data experimentally support our conclusion that the 3.9-kb start site has been introduced into the mammalian 4-GT gene to accommodate the recruited role of 4-GT in lactose biosynthesis.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				J. Zhou, Y. Wei, D. Liu, X. Ge, F. Zhou, X. Yun, J. Jiang, and J. Gu Identification of {beta}1,4GalT II as a Target Gene of p53-mediated HeLa Cell Apoptosis J. Biochem., April 1, 2008; 143(4): 547 - 554. [Abstract] [Full Text] [PDF]

				M. Sekine, C. Taya, H. Shitara, Y. Kikkawa, N. Akamatsu, M. Kotani, M. Miyazaki, A. Suzuki, and H. Yonekawa The cis-Regulatory Element Gsl5 Is Indispensable for Proximal Straight Tubule Cell-specific Transcription of Core 2 beta-1,6-N-Acetylglucosaminyltransferase in the Mouse Kidney J. Biol. Chem., January 13, 2006; 281(2): 1008 - 1015. [Abstract] [Full Text] [PDF]

				J. J. Garcia-Vallejo, W. van Dijk, I. van Die, and S. I. Gringhuis Tumor Necrosis Factor-{alpha} Up-regulates the Expression of {beta}1,4-Galactosyltransferase I in Primary Human Endothelial Cells by mRNA Stabilization J. Biol. Chem., April 1, 2005; 280(13): 12676 - 12682. [Abstract] [Full Text] [PDF]

				T. Sato and K. Furukawa Transcriptional Regulation of the Human {beta}-1,4-Galactosyltransferase V Gene in Cancer Cells: ESSENTIAL ROLE OF TRANSCRIPTION FACTOR Sp1 J. Biol. Chem., September 17, 2004; 279(38): 39574 - 39583. [Abstract] [Full Text] [PDF]

				V. R. Falkenberg, K. Alvarez, C. Roman, and N. Fregien Multiple transcription initiation and alternative splicing in the 5' untranslated region of the core 2 {beta}1-6 N-acetylglucosaminyltransferase I gene Glycobiology, June 1, 2003; 13(6): 411 - 418. [Abstract] [Full Text] [PDF]

				M. Charron, J. N. DeCerbo, and W. W. Wright A GC-Box Within the Proximal Promoter Region of the Rat Cathepsin L Gene Activates Transcription in Sertoli Cells of Sexually Mature Rats Biol Reprod, May 1, 2003; 68(5): 1649 - 1656. [Abstract] [Full Text] [PDF]

				A. Seppo, P. Matani, M. Sharrow, and M. Tiemeyer Induction of neuron-specific glycosylation by Tollo/Toll-8, a Drosophila Toll-like receptor expressed in non-neural cells Development, April 1, 2003; 130(7): 1439 - 1448. [Abstract] [Full Text] [PDF]

				R. Kane, J. Murtagh, D. Finlay, A. Marti, R. Jaggi, D. Blatchford, C. Wilde, and F. Martin Transcription Factor NFIC Undergoes N-Glycosylation during Early Mammary Gland Involution J. Biol. Chem., July 12, 2002; 277(29): 25893 - 25903. [Abstract] [Full Text] [PDF]

				S. S. Mukhopadhyay, S. L. Wyszomierski, R. M. Gronostajski, and J. M. Rosen Differential Interactions of Specific Nuclear Factor I Isoforms with the Glucocorticoid Receptor and STAT5 in the Cooperative Regulation of WAP Gene Transcription Mol. Cell. Biol., October 15, 2001; 21(20): 6859 - 6869. [Abstract] [Full Text] [PDF]

				A. R. Tovar, E. Becerril, R. Hernandez-Pando, G. Lopez, A. Suryawan, S. Desantiago, S. M. Hutson, and N. Torres Localization and expression of BCAT during pregnancy and lactation in the rat mammary gland Am J Physiol Endocrinol Metab, March 1, 2001; 280(3): E480 - E488. [Abstract] [Full Text] [PDF]

				Y. Yamaguchi, Y. Ikeda, T. Takahashi, H. Ihara, T. Tanaka, C. Sasho, N. Uozumi, S. Yanagidani, S. Inoue, J. Fujii, et al. Genomic structure and promoter analysis of the human {alpha}1,6-fucosyltransferase gene (FUT8) Glycobiology, June 1, 2000; 10(6): 637 - 643. [Abstract] [Full Text] [PDF]

				S. A. Wuensch, R. Y. Huang, J. Ewing, X. Liang, and J. T. Y. Lau Murine B cell differentiation is accompanied by programmed expression of multiple novel {beta}-galactoside {alpha}2,6-sialyltransferase mRNA forms Glycobiology, January 1, 2000; 10(1): 67 - 75. [Abstract] [Full Text] [PDF]

				M. Charron, N. L. Shaper, B. Rajput, and J. H. Shaper A Novel 14-Base-Pair Regulatory Element Is Essential for In Vivo Expression of Murine beta 4-Galactosyltransferase-I in Late Pachytene Spermatocytes and Round Spermatids Mol. Cell. Biol., August 1, 1999; 19(8): 5823 - 5832. [Abstract] [Full Text] [PDF]

				M. Charron, J. H. Shaper, and N. L. Shaper The increased level of beta 1,4-galactosyltransferase required for lactose biosynthesis is achieved in part by translational control PNAS, December 8, 1998; 95(25): 14805 - 14810. [Abstract] [Full Text] [PDF]

				T. Schwientek, R. Almeida, S. B. Levery, E. H. Holmes, E. Bennett, and H. Clausen Cloning of a Novel Member of the UDP-Galactose:beta -N-Acetylglucosamine beta 1,4-Galactosyltransferase Family, beta 4Gal-T4, Involved in Glycosphingolipid Biosynthesis J. Biol. Chem., November 6, 1998; 273(45): 29331 - 29340. [Abstract] [Full Text] [PDF]

				T. Sato, K. Furukawa, H. Bakker, D. H. Van den Eijnden, and I. Van Die Molecular cloning of a human cDNA encoding beta -1,4-galactosyltransferase with 37% identity to mammalian UDP-Gal:GlcNAc beta -1,4-galactosyltransferase PNAS, January 20, 1998; 95(2): 472 - 477. [Abstract] [Full Text] [PDF]

				M.A. Kukuruzinska and K. Lennon Protein N-Glycosylation: Molecular Genetics and Functional Significance Critical Reviews in Oral Biology & Medicine, January 1, 1998; 9(4): 415 - 448. [Abstract] [Full Text] [PDF]

				N. L. Shaper, J. A. Meurer, D. H. Joziasse, T-D. D. Chou, E. J. Smith, R. L. Schnaar, and J. H. Shaper The Chicken Genome Contains Two Functional Nonallelic beta 1,4-Galactosyltransferase Genes. CHROMOSOMAL ASSIGNMENT TO SYNTENIC REGIONS TRACKS FATE OF THE TWO GENE LINEAGES IN THE HUMAN GENOME J. Biol. Chem., December 12, 1997; 272(50): 31389 - 31399. [Abstract] [Full Text] [PDF]

				M. Sekine, K. Nara, and A. Suzuki Tissue-specific Regulation of Mouse Core 2 beta -1,6-N-Acetylglucosaminyltransferase J. Biol. Chem., October 24, 1997; 272(43): 27246 - 27252. [Abstract] [Full Text] [PDF]

				S.-L. Li, A. J. Valente, S.-J. Zhao, and R. A. Clark PU.1 Is Essential for p47phox Promoter Activity in Myeloid Cells J. Biol. Chem., July 11, 1997; 272(28): 17802 - 17809. [Abstract] [Full Text] [PDF]

				E. E.M. Furlong, N. K. Keon, F. D. Thornton, T. Rein, and F. Martin Expression of a 74-kDa Nuclear Factor 1(NF1) Protein Is Induced in Mouse Mammary Gland Involution. INVOLUTION-ENHANCED OCCUPATION OF A TWIN NF1 BINDING ELEMENT IN THE TESTOSTERONE-REPRESSED PROSTATE MESSAGE-2/CLUSTERIN PROMOTER J. Biol. Chem., November 22, 1996; 271(47): 29688 - 29697. [Abstract] [Full Text] [PDF]