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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Base Sequence
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DNA Methylation
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DNA Primers
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DNA-Binding Proteins / physiology*
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Down-Regulation
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Electrophoretic Mobility Shift Assay
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HEK293 Cells
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Humans
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Ikaros Transcription Factor / physiology*
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Lymphocytes / immunology
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Promoter Regions, Genetic*
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Real-Time Polymerase Chain Reaction
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Transcription, Genetic*
Substances
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DNA Primers
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DNA-Binding Proteins
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IKZF1 protein, human
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V(D)J recombination activating protein 2
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Ikaros Transcription Factor
Grants and funding
This work was supported by the Polish Ministry of Science and Higher Education/National Science Centre (grant N N401 049138). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.