Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/10365
New insights on the transcriptional regulation of CD69 gene through a potent enhancer located in the conserved non-coding sequence 2.
Laguna, Teresa ISCIII | Notario, Laura ISCIII | Pippa, Raffaella | Gomez Fontela, Miguel ISCIII | Vázquez, Berta N | Maicas, Miren | Aguilera-Montilla, Noemí | Corbí, Ángel L | Odero, María D | Lauzurica, Pilar ISCIII
Mol Immunol . 2015 Aug;66(2):171-9.
The CD69 type II C-type lectin is one of the earliest indicators of leukocyte activation acting in lymphocyte migration and cytokine secretion. CD69 expression in hematopoietic lineage undergoes rapid changes depending on the cell-lineage, the activation state or the localization of the cell where it is expressed, suggesting a complex and tightly controlled regulation. Here we provide new insights on the transcriptional regulation of CD69 gene in mammal species. Through in silico studies, we analyzed several regulatory features of the 4 upstream conserved non-coding sequences (CNS 1-4) previously described, confirming a major function of CNS2 in the transcriptional regulation of CD69. In addition, multiple transcription binding sites are identified in the CNS2 region by DNA cross-species conservation analysis. By functional approaches we defined a core region of 226bp located within CNS2 as the main enhancer element of CD69 transcription in the hematopoietic cells analyzed. By chromatin immunoprecipitation, binding of RUNX1 to the core-CNS2 was shown in a T cell line. In addition, we found an activating but not essential role of RUNX1 in CD69 gene transcription by site-directed mutagenesis and RNA silencing, probably through the interaction with this potent enhancer specifically in the hematopoietic lineage. In summary, in this study we contribute with new evidences to the landscape of the transcriptional regulation of the CD69 gene.
5' Flanking Region | Enhancer Elements, Genetic | Gene Expression Regulation | Transcription, Genetic | Amino Acid Sequence | Animals | Antigens, CD | Antigens, Differentiation, T-Lymphocyte | Binding Sites | Cell Line, Tumor | Conserved Sequence | Core Binding Factor Alpha 2 Subunit | Genes, Reporter | Humans | Jurkat Cells | K562 Cells | Lectins, C-Type | Luciferases | Molecular Sequence Data | Protein Binding | Transfection | Transgenes
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