Show simple item record

dc.contributor.authorRedondo-Anton, Jennifer 
dc.contributor.authorGomez Fontela, Miguel 
dc.contributor.authorNotario, Laura 
dc.contributor.authorTorres-Ruiz Raul, Torres-Ruiz Raul 
dc.contributor.authorRodríguez-Perales, Sandra
dc.contributor.authorLorente, Elena 
dc.contributor.authorLauzurica, Pilar
dc.identifier.citationFront Genet. 2020 Oct 27;11:552949.es_ES
dc.description.abstractThe 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.es_ES
dc.description.sponsorshipThe study was supported by the Instituto de Salud Carlos III MPY1346/16, MPY127/19 and Comunidad de Madrid S2018/BAA-4480 Biopieltec-CM. JR-A was supported by AESI MPY1346/16. MGF was supported by a pre-doctoral fellowship (FPU, FPU 15/05605) from the Spanish Ministry of Education, Culture and Sports (MECD). SR-P and RT-R were supported by grants from the Spanish National Research and Development Plan, Instituto de Salud Carlos III, and FEDER (PI17/02303 and DTS19/00111) and AEI/MICIU EXPLORA Project BIO2017-91272-EXP. RT-R was also supported by a postdoctoral fellowship from the Asociación Española Contra el Cáncer (AECC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.es_ES
dc.publisherFrontiers Media es_ES
dc.subjectEnhancer-derived RNA (eRNA)es_ES
dc.subjectImmune regulationes_ES
dc.subjectTranscriptional regulation.es_ES
dc.titleFunctional Characterization of a Dual Enhancer/Promoter Regulatory Element Leading Human CD69 Expression.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.doi10.3389/fgene.2020.552949. eCollection 2020es_ES
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderComunidad de Madrid (España) 
dc.contributor.funderMinisterio de Educación, Cultura y Deporte (España) 
dc.contributor.funderAsociación Española Contra el Cáncer 
dc.identifier.journalFrontiers in Geneticses_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FPU 15/05605es_ES
dc.rights.accessRightsopen accesses_ES

Files in this item

Acceso Abierto
Acceso Abierto

This item appears in the following Collection(s)

Show simple item record

Atribución 4.0 Internacional
This item is licensed under a: Atribución 4.0 Internacional