Core 2 ß1,6-N-acetylglucosaminyltransferase-I , crucial for P-selectin ligand expression is controlled by a distal enhancer regulated by STAT4 and T-bet in CD4+ T helper cells 1

Mardahl, Maibritt; Schröter, Micha F.; Engelbert, Dirk; Pink, Matthias; Sperandio, Markus; Syrbe, Uta

doi:10.1016/j.molimm.2016.08.001

Cited by 3 publications

(3 citation statements)

References 33 publications

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“…Epigenetic control is supposed to be relevant in many cases [47,48], while other emerging mechanisms controlling gene expression, such as the presence of regulatory RNA sequence and or RNA binding proteins [49], are, as yet, unexplored. At present, data are available about promoter sequences and potential regulatory elements operating in various tissues [50,51,52,53,54,55,56,57], while those actually involved in gastrointestinal cancer are described in very few cases [43,58,59,60,61]. This is a very promising field of research since a bidirectional relationship may exist between the expression of sLe antigens and the mechanisms controlling cell growth.…”

Section: Regulation Of Slea and Slexmentioning

confidence: 99%

Selectin Ligands Sialyl-Lewis a and Sialyl-Lewis x in Gastrointestinal Cancers

Trinchera

Aronica

Dall’Olio

2017

Biology

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The tetrasaccharide structures Siaα2,3Galβ1,3(Fucα1,4)GlcNAc and Siaα2,3Galβ1,4(Fucα1,3)GlcNAc constitute the epitopes of the carbohydrate antigens sialyl-Lewis a (sLea) and sialyl-Lewis x (sLex), respectively, and are the minimal requirement for selectin binding to their counter-receptors. Interaction of sLex expressed on the cell surface of leucocytes with E-selectin on endothelial cells allows their arrest and promotes their extravasation. Similarly, the rolling of cancer cells ectopically expressing the selectin ligands on endothelial cells is potentially a crucial step favoring the metastatic process. In this review, we focus on the biosynthetic steps giving rise to selectin ligand expression in cell lines and native tissues of gastrointestinal origin, trying to understand whether and how they are deregulated in cancer. We also discuss the use of such molecules in the diagnosis of gastrointestinal cancers, particularly in light of recent data questioning the ability of colon cancers to express sLea and the possible use of circulating sLex in the early detection of pancreatic cancer. Finally, we reviewed the data dealing with the mechanisms that link selectin ligand expression in gastrointestinal cells to cancer malignancy. This promising research field seems to require additional data on native patient tissues to reach more definitive conclusions.

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Section: Regulation Of Slea and Slexmentioning

confidence: 99%

Selectin Ligands Sialyl-Lewis a and Sialyl-Lewis x in Gastrointestinal Cancers

Trinchera

Aronica

Dall’Olio

2017

Biology

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“…GCNT1 is a glycosyltransferase involved in pathways related to metabolism of proteins, and it has several functions involved in immune response. One recent study demonstrated that the protein product of GCNT1 , core 2 ß1,6- N -acetylglucosaminyltransferase-I (C2GlcNAcT-I), is necessary not only for the synthesis of P-selectin ligands in neutrophils and T helper 1 (Th1) cells but also for the homing of Th1 cells into sites of inflammation ( 27 ). Additional roles of GCNT1 include partially controlling lymphocyte trafficking into lymph nodes and regulating B cell differentiation via formation and extension of core 2 O-glycans ( 28 , 29 ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome-wide association study of circulating IgE levels identifies novel targets for asthma and allergic diseases

et al. 2023

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Measurement of circulating immunoglobulin E (IgE) concentration is helpful for diagnosing and treating asthma and allergic diseases. Identifying gene expression signatures associated with IgE might elucidate novel pathways for IgE regulation. To this end, we performed a discovery transcriptome-wide association study to identify differentially expressed genes associated with circulating IgE levels in whole-blood derived RNA from 5,345 participants in the Framingham Heart Study across 17,873 mRNA gene-level transcripts. We identified 216 significant transcripts at a false discovery rate <0.05. We conducted replication using the meta-analysis of two independent external studies: the Childhood Asthma Management Program (n=610) and the Genetic Epidemiology of Asthma in Costa Rica Study (n=326); we then reversed the discovery and replication cohorts, which revealed 59 significant genes that replicated in both directions. Gene ontology analysis revealed that many of these genes were implicated in immune function pathways, including defense response, inflammatory response, and cytokine production. Mendelian randomization (MR) analysis revealed four genes (CLC, CCDC21, S100A13, and GCNT1) as putatively causal (p<0.05) regulators of IgE levels. GCNT1 (beta=1.5, p=0.01)—which is a top result in the MR analysis of expression in relation to asthma and allergic diseases—plays a role in regulating T helper type 1 cell homing, lymphocyte trafficking, and B cell differentiation. Our findings build upon prior knowledge of IgE regulation and provide a deeper understanding of underlying molecular mechanisms. The IgE-associated genes that we identified—particularly those implicated in MR analysis—can be explored as promising therapeutic targets for asthma and IgE-related diseases.

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“…GCNT1 is a glycosyltransferase involved in pathways related to metabolism of proteins, and it has several functions involved in immune response. One recent study demonstrated that the protein product of GCNT1 , core 2 ß1,6- N -acetylglucosaminyltransferase-I (C2GlcNAcT-I), is necessary not only for the synthesis of P-selectin ligands in neutrophils and T helper 1 (Th1) cells but also for the homing of Th1 cells into sites of inflammation 28 . Additional roles of GCNT1 include partially controlling lymphocyte trafficking into lymph nodes and regulating B cell differentiation via formation and extension of core 2 O-glycans 29,30 .…”

Section: Discussionmentioning

confidence: 99%

Transcriptome-wide Association Study of Circulating IgE Levels Identifies Novel Targets for Asthma and Allergic Diseases

Kathryn¹,

Huan²,

Heon³

et al. 2020

Preprint

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Measurement of circulating immunoglobulin E (IgE) concentration is helpful for diagnosing and treating asthma and allergic diseases. Identifying gene expression signatures associated with IgE might elucidate novel pathways for IgE regulation. To this end, we performed a discovery transcriptome-wide association study (TWAS) to identify differentially expressed genes associated with circulating IgE levels in whole-blood derived RNA from 5,345 participants in the Framingham Heart Study (FHS) across 17,873 mRNA gene-level transcripts. We identified 216 significant transcripts at a false discovery rate (FDR)<0.05. We conducted replication using the meta-analysis of two independent external studies: the Childhood Asthma Management Program (n=610) and the Genetic Epidemiology of Asthma in Costa Rica Study (n=326); we then reversed the discovery and replication cohorts, which revealed 59 significant genes that bi-directionally replicated. Gene ontology analysis revealed that many of these genes were implicated in immune function pathways, including defense response, inflammatory response, and cytokine production. Mendelian randomization (MR) analysis revealed four genes (CLC, CCDC21, S100A13, and GCNT1) as putatively causal (p<0.05) regulators of IgE levels. GCNT1 (beta=1.5, p=0.01), which is a top result in the MR analysis of expression in relation to asthma and allergic diseases, plays a role in regulating T helper type 1 (Th1) cell homing, lymphocyte trafficking, and B cell differentiation. Our findings build upon prior knowledge of IgE regulation and provide a deeper understanding of underlying molecular mechanisms. The IgE-associated genes that we identified, particularly those implicated in MR analysis, can be explored as promising therapeutic targets for asthma and IgE-related diseases.

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Core 2 ß1,6-N-acetylglucosaminyltransferase-I , crucial for P-selectin ligand expression is controlled by a distal enhancer regulated by STAT4 and T-bet in CD4+ T helper cells 1

Cited by 3 publications

References 33 publications

Selectin Ligands Sialyl-Lewis a and Sialyl-Lewis x in Gastrointestinal Cancers

Selectin Ligands Sialyl-Lewis a and Sialyl-Lewis x in Gastrointestinal Cancers

Transcriptome-wide association study of circulating IgE levels identifies novel targets for asthma and allergic diseases

Transcriptome-wide Association Study of Circulating IgE Levels Identifies Novel Targets for Asthma and Allergic Diseases

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