The Conserved Non-Coding Sequence 2 (CNS2) Enhances CD69 Transcription through Cooperation between the Transcription Factors Oct1 and RUNX1
by
Miguel G. Fontela 1
, Laura Notario 1, Elisenda Alari-Pahissa 2, Elena Lorente 1 and Pilar Lauzurica 1,*
Miguel G. Fontela 1, Laura Notario 1, Elisenda Alari-Pahissa 2, Elena Lorente 1 and Pilar Lauzurica 1,*
1
Microbiology National Center, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain
2
Department of Experimental and Health Science, University Pompeu Fabra, 08003 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Genes 2019, 10(9), 651; https://doi.org/10.3390/genes10090651
Received: 27 June 2019 / Revised: 29 July 2019 / Accepted: 23 August 2019 / Published: 28 August 2019
(This article belongs to the Section Molecular Genetics and Genomics)
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 CD69 promoter, there are four conserved noncoding regions (CNS1-4) upstream of the CD69 promoter. Furthermore, we proposed that CNS2 is the main enhancer of CD69 transcription. In the present study, we mapped the transcription factor (TF) binding sites (TFBS) from ChIP-seq databases within CNS2. Through luciferase reporter assays, we defined a ~60 bp sequence that acts as the minimum enhancer core of mouse CNS2, 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 CD69 gene transcription. In summary, we describe an enhancer core containing RUNX1 and Oct1 BS that is important for the activity of the most potent CD69 gene transcription enhancer.
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MDPI and ACS Style
Fontela, M.G.; Notario, L.; Alari-Pahissa, E.; Lorente, E.; Lauzurica, P. The Conserved Non-Coding Sequence 2 (CNS2) Enhances CD69 Transcription through Cooperation between the Transcription Factors Oct1 and RUNX1. Genes 2019, 10, 651.
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