title: Early B-cell factor 1 (EBF1) is critical for transcriptional control of SLAMF1 gene in human B cells.
abstract: 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.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Anton M
authors.initials: AM
authors.lastname: Schwartz
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Lidia V
authors.initials: LV
authors.lastname: Putlyaeva
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Milica
authors.initials: M
authors.lastname: Covich
authors.affiliation: Institute for Information Transmission Problems of the Russian Academy of Sciences, Moscow, Russia; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Klepikova
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia; School of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Kseniya A
authors.initials: KA
authors.lastname: Akulich
authors.affiliation: Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Ilya E
authors.initials: IE
authors.lastname: Vorontsov
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia; Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Kirill V
authors.initials: KV
authors.lastname: Korneev
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia; Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Sergey E
authors.initials: SE
authors.lastname: Dmitriev
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Oleg L
authors.initials: OL
authors.lastname: Polanovsky
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of National Academy of Sciences of Ukraine, Kyiv, Ukraine.
authors.forename: Svetlana P
authors.initials: SP
authors.lastname: Sidorenko
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia; Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Kulakovskiy
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia; Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia. Electronic address: kuprash@eimb.ru.
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Kuprash
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; 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 / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1 / Q000235:genetics* / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D000099232:Proto-Oncogene Protein Spi-1; D000099218:Interferon Regulatory Factor-4
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050835:Interferon Regulatory Factors; D008156:Luciferases; D016328:NF-kappa B; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D050800:STAT6 Transcription Factor; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D016329:Sp1 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; D000099218:Interferon Regulatory Factor-4; C081976:EBF1 protein, human; C512897:ELF1 protein, human; C000604059:SLAMF1 protein, human; C494101:STAT6 protein, human; C108209:SP1 protein, human; C407909:TCF3 protein, human
keywords: B cell; EBF1; RNA isoform; SLAMF; Transcriptional regulation; Trascription factor