Early B-cell factor 1 (EBF1) is critical for transcriptional control of SLAMF1 gene in human B cells.
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.
['Schwartz|Anton M|AM|', 'Putlyaeva|Lidia V|LV|', 'Covich|Milica|M|', 'Klepikova|Anna V|AV|', 'Akulich|Kseniya A|KA|', 'Vorontsov|Ilya E|IE|', 'Korneev|Kirill V|KV|', 'Dmitriev|Sergey E|SE|', 'Polanovsky|Oleg L|OL|', 'Sidorenko|Svetlana P|SP|', 'Kulakovskiy|Ivan V|IV|', 'Kuprash|Dmitry V|DV|']
D001402:B-Lymphocytes D051792:Basic Helix-Loop-Helix Transcription Factors D001665:Binding Sites D045744:Cell Line, Tumor D004742:Enhancer Elements, Genetic D005786:Gene Expression Regulation D017930:Genes, Reporter D057809:HEK293 Cells D006801:Humans D050835:Interferon Regulatory Factors D008156:Luciferases D009154:Mutation D016328:NF-kappa B D009687:Nuclear Proteins D061251:Primary Cell Culture D011401:Promoter Regions, Genetic D011485:Protein Binding D011518:Proto-Oncogene Proteins D050800:STAT6 Transcription Factor D015398:Signal Transduction D000071177:Signaling Lymphocytic Activation Molecule Family Member 1 D016329:Sp1 Transcription Factor D015534:Trans-Activators D014157:Transcription Factors D014158:Transcription, Genetic
EBF1 B cell RNA isoform SLAMF Transcriptional regulation Trascription factor