Title

Transcriptional regulation of the core 2 beta 1,6 N-acetylglucosaminyltransferase I gene

Date of Award

2006

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Molecular Cell and Developmental Biology

First Committee Member

Nevis Fregien, Committee Chair

Abstract

This manuscript describes the genomic organization and transcriptional regulation of one important glycosyltransferase, the core 2 beta1,6 N-acetylglucosaminyltransferase I (C2GnTI). C2GnTI is responsible for the synthesis of core 2 [Galbeta1→3(GlcNAcbeta1→6)GalNAc] branches, forming a beta1,6 linkage between N-acetylglucosamine and the core 1 branch in O-linked oligosaccharides. Precise regulation of core 2 branched oligosaccharides is essential to the normal function and behavior of both lymphocytes and mucin-producing epithelial cells. In humans, C2GnTI is expressed from at least four promoters that synthesize at least 5 different mRNAs, each of which vary in the 5' untranslated region (UTR). C2GnTI is expressed in many different tissues, and the level of expression varies from tissue to tissue. The most widely used of these promoters will be referred to as promoter 2, and is expressed in at least 20 different tissues. The other three promoters are used in a more tissue-specific manner. C2GnTI promoter 2 is very G-C rich, and contains nine Sp1 binding sites within the minimal promoter region. The transcription factor Sp1 is essential for transcription of C2GnTI in both mesodermally derived T-cells (Jurkat) and in endodermal mucin producing epithelial cells (NCI H292). In Jurkat cells, all nine of the Sp1 binding sites within the minimal promoter region contribute to transcription, and there is a linear relationship between the number of Sp1 sites and the transcriptional activity of the promoter. In NCI H292 cells, only four of these Sp1 binding sites are essential for transcription. Chromatin immunoprecipitation (ChIP) assays show that Sp1 binds to promoter 2 in vivo using NCI H292 cells.

Keywords

Biology, Molecular; Biology, Cell; Health Sciences, Immunology; Health Sciences, Oncology

Link to Full Text

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