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

Cindy Wavelet-Vermuse (1) , Sophie Groux-Degroote (1) , Dorothée Vicogne (1) , Virginie Cogez (1) , Giulia Venturi (2) , Marco Trinchera (3) , Guillaume Brysbaert (1) , Marie-Ange Krzewinski-Recchi (1) , Elsa Hadj Bachir (4) , Céline Schulz (1) , Audrey Vincent (4) , Isabelle van Seuningen (4) , Anne Harduin-Lepers (1)

1 UGSF - Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
2 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
3 Uninsubria - Universitá degli Studi dell’Insubria = University of Insubria [Varese]
4 CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277

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.

Mots clés: Transcriptional regulation; Core promoter; ETS1; Colon; B4GALNT2

Domaines: Biochimie, Biologie Moléculaire

Cindy Wavelet-Vermuse, Sophie Groux-Degroote, Dorothée Vicogne, Virginie Cogez, Giulia Venturi, et al.. Analysis of the proximal promoter of the human colon-specific B4GALNT2 (Sda synthase) gene: B4GALNT2 is transcriptionally regulated by ETS1. Biochimica et Biophysica Acta - Gene Regulatory Mechanisms , 2021, 1864 (11-12), pp.194747. ⟨10.1016/j.bbagrm.2021.194747⟩. ⟨hal-03345208⟩