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Analysis of the proximal promoter of the human colon-specific B4GALNT2 (Sda synthase) gene: B4GALNT2 is transcriptionally regulated by ETS1
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms ( IF 2.6 ) Pub Date : 2021-09-07 , DOI: 10.1016/j.bbagrm.2021.194747
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
Affiliation  

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.



中文翻译:


人结肠特异性B4GALNT2(Sda合酶)基因近端启动子分析:B4GALNT2受ETS1转录调控



背景:Sd a抗原和相应的生物合成酶B4GALNT2主要在正常结肠粘膜中表达,在结肠癌组织中不同程度地下调。尽管它们的表达谱已得到充分研究,但对其潜在的调控机制知之甚少。方法:为了阐明 Sd a在人胃肠道中表达的分子基础,我们研究了人B4GALNT2基因的转录调控。使用荧光素酶测定描绘近端启动子区域,并通过几个转录因子的瞬时过表达和沉默来鉴定必需的式作用因子。结果:限制在B4GALNT2短型转录变体上游的 -72 至 +12 区域的短顺调节区包含驱动人B4GALNT2表达的基本启动子活性,无论细胞类型如何。我们进一步表明, B4GALNT2转录激活主要需要 ETS1,其次需要 SP1。结论:本文提出的结果有望为更好地理解B4GALNT2调控机制提供线索。

更新日期:2021-09-15
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