Early B-cell factor 1 (EBF1) is critical for transcriptional control of SLAMF1 gene in human B cells

• Published in: Biochimica et biophysica acta Vol. 1859; no. 10; pp. 1259 - 1268
• Main Authors: Schwartz, Anton M., Putlyaeva, Lidia V., Covich, Milica, Klepikova, Anna V., Akulich, Kseniya A., Vorontsov, Ilya E., Korneev, Kirill V., Dmitriev, Sergey E., Polanovsky, Oleg L., Sidorenko, Svetlana P., Kulakovskiy, Ivan V., Kuprash, Dmitry V.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2016
• Subjects: B cell; B-Lymphocytes - cytology; B-Lymphocytes - metabolism; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Binding Sites; Cell Line, Tumor; EBF1; Enhancer Elements, Genetic; Gene Expression Regulation; Genes, Reporter; HEK293 Cells; Humans; Interferon Regulatory Factors - genetics; Interferon Regulatory Factors - metabolism; Luciferases - genetics; Mutation; NF-kappa B - genetics; NF-kappa B - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Primary Cell Culture; Promoter Regions, Genetic; Protein Binding; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; RNA isoform; Signal Transduction; Signaling Lymphocytic Activation Molecule Family Member 1 - genetics; Signaling Lymphocytic Activation Molecule Family Member 1 - metabolism; SLAMF; Sp1 Transcription Factor - genetics; Sp1 Transcription Factor - metabolism; STAT6 Transcription Factor - genetics; STAT6 Transcription Factor - metabolism; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; Transcriptional regulation; Trascription factor; EBF1; B cell; RNA isoform; Trascription factor; SLAMF; Transcriptional regulation
• ISSN: 1874-9399; 0006-3002; 1876-4320
• DOI: 10.1016/j.bbagrm.2016.07.004

Signaling lymphocytic activation molecule family member 1 (SLAMF1)/CD150 is a co-stimulatory receptor expressed on a variety of hematopoietic cells, in particular on mature lymphocytes activated by specific antigen, costimulation and cytokines. Changes in CD150 expression level have been reported in association with autoimmunity and with B-cell chronic lymphocytic leukemia. We characterized the core promoter for SLAMF1 gene in human B-cell lines and explored binding sites for a number of transcription factors involved in B cell differentiation and activation. Mutations of SP1, STAT6, IRF4, NF-kB, ELF1, TCF3, and SPI1/PU.1 sites resulted in significantly decreased promoter activity of varying magnitude, depending on the cell line tested. The most profound effect on the promoter strength was observed upon mutation of the binding site for Early B-cell factor 1 (EBF1). This mutation produced a 10–20 fold drop in promoter activity and pinpointed EBF1 as the master regulator of human SLAMF1 gene in B cells. We also identified three potent transcriptional enhancers in human SLAMF1 locus, each containing functional EBF1 binding sites. Thus, EBF1 interacts with specific binding sites located both in the promoter and in the enhancer regions of the SLAMF1 gene and is critical for its expression in human B cells. •SLAMF1 promoter contains binding sites for several transcription factors involved in B cell differentiation and activation.•Mutation of the binding site for EBF1 results in a most profound effect on the SLAMF1 promoter strength.•At least 3 transcriptional enhancers in human SLAMF1 locus contain functional EBF1 binding sites.•Of other SLAM family genes, SLAMF3, 4, 5, 7 are also controlled by EBF1.