Characterization of promoter elements directing Mona/Gads molecular adapter expression in T and myelomonocytic cells: involvement of the AML-1 transcription factor
Abstract
Monocytic adaptor (Mona, also called Gads) is a molecular adaptor implicated in T cell activation and macrophage differentiation. The objective of this study was to identify elements regulating specific expression of Mona/Gads in human T cell and myelomonocytic cell lines. We first confirmed that the −2000 to +150 genomic region relative to the Mona gene transcription start site is sufficient to direct specific reporter gene expression in T cell lines, Jurkat, and MOLT-4 and in the immature myeloid cell lines, KG1a and RC2A. Deletion analysis and electrophoresis mobility shift assay identified several cis regulatory elements: overlapping initiator sequences, one interferon response factor-2 (IRF-2)-binding site at position −154, one GC box recognized by Sp1 and Sp3 at position −52, and two acute myeloid leukemia (AML)-1 binding sites at positions −70 and −13. Site-directed mutagenesis experiments indicated a key role of AML-1 for driving Mona expression in T cells and myeloid cells, and involvement of Sp1/Sp3 and IRF-2 transcription factors to modulate Mona expression in a cell-specific manner.
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Previous studies found IRF2 activates transcription of some genes involved in the innate immune response.
“Previous studies found IRF2 activates transcription of some genes involved in the innate immune response (23, 44 -46).”
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- Authors
- Guyot, B., & Mouchiroud, G.
- Affiliations
- Lyon 1 Université (FR)
- Corresponding author
- Mouchiroud, G
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-02-01
- Volume
- 73
- Issue
- 2
- Pages
- 263-272
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W2170619973
- Cited by
- 5
- References
- 48
- Citations by year
- 2023: 1 · 2021: 1
- FWCI
- 0.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Centre National de la Recherche Scientifique
- Ligue Nationale contre le Cancer
- Fondation Mérieux and Association pour la Recherche contre le Cancer
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- promoter elements, IRF2, Sp1 binding site, T cell activation, myelomonocytic cells, transcriptional regulation, macrophage differentiation, Jurkat cells, MOLT-4 cells, KG1a cells
- MeSH terms
- Base Sequence, Carrier Proteins, Cells, Cultured, DNA-Binding Proteins, Humans, Molecular Sequence Data, Promoter Regions, Genetic, Proto-Oncogene Proteins, Repressor Proteins, T-Lymphocytes, Transcription Factors, Transcription, Genetic, Sp1 Transcription Factor, 5' Untranslated Regions, 5' Flanking Region, Adaptor Proteins, Signal Transducing, Core Binding Factor Alpha 2 Subunit, Interferon Regulatory Factor-2, Sp3 Transcription Factor
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