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Sp1对淋巴细胞和上皮细胞中核心2 β1,6 N-乙酰葡糖胺基转移酶-I转录的调控

Control of core 2 beta1,6 N-acetylglucosaminyltransferase-I transcription by Sp1 in lymphocytes and epithelial cells.

作者信息

Falkenberg V Rebecca, Fregien Nevis

机构信息

Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

出版信息

Glycoconj J. 2007 Dec;24(9):511-9. doi: 10.1007/s10719-007-9043-2. Epub 2007 May 26.

Abstract

Core 2 beta1,6 N-acetylglucosaminyltransferase-I (C2GnT-I) catalyzes the synthesis of one of the major core structures in GalNAc alpha-Ser/Thr O-linked oligosaccharides, the core 2 branch. The production of the core 2 branch is required for the synthesis of glycoforms that are important for the cellular functions of lymphocytes, mucin-producing epithelial cells and other cell types. Therefore, proper molecular control of C2GnT-I expression is very important for different types of cells. C2GnT-I is transcribed from 4 promoters, with promoter 2 being the major promoter. C2GnT-I promoter 2 lacks a TATA box and is very GC rich. In this study, the analysis of this promoter finds that the transcription factor Sp1 is essential for transcription of C2GnT-I 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 three of these Sp1 binding sites are required for transcription from promoter 2. Chromatin immunoprecipitation confirms that Sp1 binds to promoter 2 in NCI H292 cells in vivo.

摘要

核心2β1,6 - N - 乙酰葡糖胺基转移酶-I(C2GnT - I)催化合成GalNAcα - Ser/Thr O - 连接寡糖中的一种主要核心结构,即核心2分支。核心2分支的产生是合成对淋巴细胞、产生粘蛋白的上皮细胞及其他细胞类型的细胞功能很重要的糖型所必需的。因此,对C2GnT - I表达进行适当的分子调控对不同类型的细胞非常重要。C2GnT - I由4个启动子转录,其中启动子2是主要启动子。C2GnT - I启动子2缺乏TATA框且富含GC。在本研究中,对该启动子的分析发现转录因子Sp1对于中胚层来源的T细胞(Jurkat细胞)和内胚层产生粘蛋白的上皮细胞(NCI H292细胞)中C2GnT - I的转录至关重要。在Jurkat细胞中,最小启动子区域内的所有9个Sp1结合位点都对转录有贡献,并且Sp1位点的数量与启动子的转录活性之间存在线性关系。在NCI H292细胞中,启动子2转录仅需要这些Sp1结合位点中的3个。染色质免疫沉淀证实Sp1在体内与NCI H292细胞中的启动子2结合。

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