Functional Characterization of a Dual Enhancer/Promoter Regulatory Element Leading Human CD69 Expression

Frontiers in Genetics
Jennifer Redondo-AntónPilar Lauzurica

Abstract

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 transcript...Continue Reading

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Methods Mentioned

BETA
chemical modification
proximity ligation
transfection
Flow Cytometry
PMA
PCR
Immunoprecipitation
electrophoresis
Chip
PCRs

Software Mentioned

Vista
Blast Primer
FlowJo
GraphPad Prism
FACSDiva
Cap Analysis

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