Analysis of the proximal promoter of the human colon-specific B4GALNT2 (Sda synthase) gene: B4GALNT2 is transcriptionally regulated by ETS1

• Published in: Biochimica et biophysica acta. Gene regulatory mechanisms Vol. 1864; no. 11-12; p. 194747
• Main Authors: Wavelet-Vermuse, Cindy, Groux-Degroote, Sophie, Vicogne, Dorothée, Cogez, Virginie, Venturi, Giulia, Trinchera, Marco, Brysbaert, Guillaume, Krzewinski-Recchi, Marie-Ange, Hadj Bachir, Elsa, Schulz, Céline, Vincent, Audrey, Van Seuningen, Isabelle, Harduin-Lepers, Anne
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2021; Elsevier
• Subjects: B4GALNT2; Biochemistry, Molecular Biology; Colon; Core promoter; ETS1; HT29 Cells; Humans; Intestinal Mucosa; Life Sciences; N-Acetylgalactosaminyltransferases - genetics; N-Acetylgalactosaminyltransferases - metabolism; Oligosaccharides - biosynthesis; Promoter Regions, Genetic; Proto-Oncogene Protein c-ets-1 - metabolism; Sp1 Transcription Factor - metabolism; Transcriptional Activation; Transcriptional regulation; Core promoter; Colon; Transcriptional regulation; ETS1; B4GALNT2
• ISSN: 1874-9399; 1876-4320
• DOI: 10.1016/j.bbagrm.2021.194747

Background: The Sda antigen and corresponding biosynthetic enzyme B4GALNT2 are primarily expressed in normal colonic mucosa and are down-regulated to a variable degree in colon cancer tissues. Although their expression profile is well studied, little is known about the underlying regulatory mechanisms. Methods: To clarify the molecular basis of Sda expression in the human gastrointestinal tract, we investigated the transcriptional regulation of the human B4GALNT2 gene. The proximal promoter region was delineated using luciferase assays and essential trans-acting factors were identified through transient overexpression and silencing of several transcription factors. Results: A short cis-regulatory region restricted to the −72 to +12 area upstream of the B4GALNT2 short-type transcript variant contained the essential promoter activity that drives the expression of the human B4GALNT2 regardless of the cell type. We further showed that B4GALNT2 transcriptional activation mostly requires ETS1 and to a lesser extent SP1. Conclusions: Results presented herein are expected to provide clues to better understand B4GALNT2 regulatory mechanisms. •The Sda antigen and corresponding biosynthetic enzyme B4GALNT2 are primarily expressed in normal colonic mucosa.•The Sda antigen disappear in colon cancer to the benefit of SLex.•The proximal promoter region of B4GALNT2 was delineated and essential trans-acting factors were identified.•Transcriptional activation of B4GALNT2 mostly requires ETS1 and SP1.