The Conserved Non-Coding Sequence 2 (CNS2) Enhances CD69 Transcription through Cooperation between the Transcription Factors Oct1 and RUNX1

The immune regulatory receptor CD69 is expressed upon activation in all types of leukocytes and is strongly regulated at the transcriptional level. We previously described that, in addition to the promoter, there are four conserved noncoding regions ( ) upstream of the promoter. Furthermore, we prop...

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Bibliographic Details
Published in:Genes 2019-08, Vol.10 (9), p.651
Main Authors: Fontela, Miguel G, Notario, Laura, Alari-Pahissa, Elisenda, Lorente, Elena, Lauzurica, Pilar
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - genetics
Antigens, CD - metabolism
Antigens, Differentiation, T-Lymphocyte - genetics
Antigens, Differentiation, T-Lymphocyte - metabolism
Binding sites
CD69 antigen
Cloning
Conserved Sequence
Consortia
Cooperation
Cooperativity
Core Binding Factor Alpha 2 Subunit - metabolism
Data mining
Enhancer Elements, Genetic
Flow cytometry
Genes
Genomes
Humans
Jurkat Cells
Lectins, C-Type - genetics
Lectins, C-Type - metabolism
Leukocytes
Lymphocytes
Mammals
Mice
Octamer Transcription Factor-1 - metabolism
Plasmids
Protein Binding
RNA, Messenger - genetics
RNA, Messenger - metabolism
Runx1 protein
siRNA
Software
Transcription factors
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Description
Summary:The immune regulatory receptor CD69 is expressed upon activation in all types of leukocytes and is strongly regulated at the transcriptional level. We previously described that, in addition to the promoter, there are four conserved noncoding regions ( ) upstream of the promoter. Furthermore, we proposed that is the main enhancer of transcription. In the present study, we mapped the transcription factor (TF) binding sites (TFBS) from ChIP-seq databases within . Through luciferase reporter assays, we defined a ~60 bp sequence that acts as the minimum enhancer core of mouse , which includes the Oct1 TFBS. This enhancer core establishes cooperative interactions with the 3' and 5' flanking regions, which contain RUNX1 BS. In agreement with the luciferase reporter data, the inhibition of RUNX1 and Oct1 TF expression by siRNA suggests that they synergistically enhance endogenous gene transcription. In summary, we describe an enhancer core containing RUNX1 and Oct1 BS that is important for the activity of the most potent gene transcription enhancer.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes10090651