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New insights on the transcriptional regulation of CD69 gene through a potent enhancer located in the conserved non-coding sequence 2
- Source :
- Repisalud, Instituto de Salud Carlos III (ISCIII), Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- 35 p.-8 fig.<br />The CD69 type II C-type lectin is one ofthe earliestindicators of leukocyte activation acting in lymphocyte migration and cytokine secretion. CD69 expression in hematopoietic lineage undergoes rapid changes depending on the cell-lineage,the activation state or the localization ofthe cell where itis expressed, suggesting a complex and tightly controlled regulation. Here we provide new insights on the transcriptional regulation of CD69 gene in mammal species. Through in silico studies, we analyzed several regulatory features of the 4 upstream conserved non-coding sequences (CNS 1–4) previously described, confirming a major function of CNS2 in the transcriptional regulation of CD69. In addition, multiple transcription binding sites are identified in the CNS2 region by DNA cross-species conservation analysis. By functional approaches we defined a core region of 226 bp located within CNS2 as the main enhancer element of CD69 transcription in the hematopoietic cells analyzed. By chromatin immunoprecipitation, binding of RUNX1 to the core-CNS2 was shown in a T cell line. In addition, we found an activating but not essential role of RUNX1 in CD69 gene transcription by site-directed mutagenesis and RNA silencing, probably through the interaction with this potent enhancer specifically in the hematopoietic lineage. In summary, in this study we contribute with new evidences to the landscape of the transcriptional regulation of the CD69 gene.<br />This work was supported by the Spanish Ministry of Economics (SAF2010-15649) and the Carlos III National Health Institute (ISCIII) – RTICC (RD12/0036/0063)
- Subjects :
- Antigens, Differentiation, T-Lymphocyte
Transcription, Genetic
5' Flanking Region
Molecular Sequence Data
Immunology
chemical and pharmacologic phenomena
Enhancer RNAs
Biology
Transfection
Conserved non-coding sequence
Jurkat Cells
Upstream activating sequence
Antigens, CD
Genes, Reporter
Transcription (biology)
Cell Line, Tumor
Enhancers
Transcriptional regulation
Animals
Humans
Lectins, C-Type
Amino Acid Sequence
Transgenes
CD69
Luciferases
Enhancer
Molecular Biology
Conserved Sequence
Genetics
Regulation of gene expression
Binding Sites
Transcription regulation
Gene regulation
Enhancer Elements, Genetic
Gene Expression Regulation
Core Binding Factor Alpha 2 Subunit
CNS
K562 Cells
Chromatin immunoprecipitation
Protein Binding
Subjects
Details
- ISSN :
- 01615890
- Volume :
- 66
- Database :
- OpenAIRE
- Journal :
- Molecular Immunology
- Accession number :
- edsair.doi.dedup.....0be67cd5edb3266fdb01c0ddd04179fc