title: Ikaros and RAG-2-mediated antisense transcription are responsible for lymphocyte-specific inactivation of NWC promoter.
abstract: Recombination activating gene-2 (RAG-2) and NWC are strongly evolutionarily conserved overlapping genes which are convergently transcribed. In non-lymphoid cells the NWC promoter is active whereas in lymphocytes it is inactive due to the DNA methylation. Analysing the mechanism responsible for lymphocyte-specific methylation and inactivation of NWC promoter we found that Ikaros, a lymphocyte-specific transcription factor, acts as a repressor of NWC promoter--thus identifying a new Ikaros target--but is insufficient for inducing its methylation which depends on the antisense transcription driven by RAG-2 promoter. Possible implications of these observations for understanding evolutionary mechanisms leading to lymphocyte specific expression of RAG genes are discussed.
authors.affiliation: Laboratory of Molecular and Cellular Immunology, Department of Tumor Immunology, Institute of Immunology and Experimental Therapy, Wrocław, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Laszkiewicz
authors.affiliation: Laboratory of Molecular and Cellular Immunology, Department of Tumor Immunology, Institute of Immunology and Experimental Therapy, Wrocław, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Bzdzion
authors.affiliation: Laboratory of Molecular and Cellular Immunology, Department of Tumor Immunology, Institute of Immunology and Experimental Therapy, Wrocław, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Kasztura
authors.affiliation: Laboratory of Molecular and Cellular Immunology, Department of Tumor Immunology, Institute of Immunology and Experimental Therapy, Wrocław, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Snieżewski
authors.affiliation: Laboratory of Molecular and Cellular Immunology, Department of Tumor Immunology, Institute of Immunology and Experimental Therapy, Wrocław, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Janik
authors.affiliation: Laboratory of Molecular and Cellular Immunology, Department of Tumor Immunology, Institute of Immunology and Experimental Therapy, Wrocław, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Kisielow
authors.affiliation: Laboratory of Molecular and Cellular Immunology, Department of Tumor Immunology, Institute of Immunology and Experimental Therapy, Wrocław, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Cebrat
mesh_terms: D001483:Base Sequence; D019175:DNA Methylation; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D057809:HEK293 Cells; D006801:Humans; D051740:Ikaros Transcription Factor / Q000502:physiology*; D008214:Lymphocytes / Q000276:immunology; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C497239:IKZF1 protein, human; C064655:V(D)J recombination activating protein 2; D051740:Ikaros Transcription Factor