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oai:repisalud.isciii.es:20.500.12105/120062024-09-27T19:12:29Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Redondo-Anton, Jennifer author Gomez Fontela, Miguel author Notario, Laura author Raul, Torres-Ruiz author Rodríguez-Perales, Sandra author Lorente, Elena author Lauzurica, Pilar author 2020-10-27 The CD69 gene encodes a C-type lectin glycoprotein with immune regulatory properties which is expressed on the cell surfaces of all activated hematopoietic cells. CD69 activation kinetics differ by developmental stage, cell linage and activating conditions, and these differences have been attributed to the participation of complex gene regulatory networks. An evolutionarily conserved regulatory element, CNS2, located 4kb upstream of the CD69 gene transcriptional start site, has been proposed as the major candidate governing the gene transcriptional activation program. To investigate the function of human CNS2, we studied the effect of its endogenous elimination via CRISPR-Cas9 on CD69 protein and mRNA expression levels in various immune cell lines. Even when the entire promoter region was maintained, CNS2-/- cells did not express CD69, thus indicating that CNS2 has promoter-like characteristics. However, like enhancers, inverted CNS2 sustained transcription, although at a diminished levels, thereby suggesting that it has dual promoter and enhancer functions. Episomal luciferase assays further suggested that both functions are combined within the CNS2 regulatory element. In addition, CNS2 directs its own bidirectional transcription into two different enhancer-derived RNAs molecules (eRNAs) which are transcribed from two independent transcriptional start sites in opposite directions. This eRNA transcription is dependent on only the enhancer sequence itself, because in the absence of the CD69 promoter, sufficient RNA polymerase II levels are maintained at CNS2 to drive eRNA expression. Here, we describe a regulatory element with overlapping promoter and enhancer functions, which is essential for CD69 gene transcriptional regulation. Front Genet. 2020 Oct 27;11:552949. 10.3389/fgene.2020.552949. eCollection 2020 1664-8021 Frontiers in Genetics 33193627 http://hdl.handle.net/20.500.12105/12006 CD69 Enhancer Enhancer-derived RNA (eRNA) Immune regulation Promoter Transcriptional regulation. Functional Characterization of a Dual Enhancer/Promoter Regulatory Element Leading Human CD69 Expression