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A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia
Published on: December 4, 2018
Selective activation of NFAT by promyelocytic leukemia protein
1Graduate Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan, ROC.
Abstract:
Promyelocytic leukemia (PML) protein is a tumor suppressor with complicated action mechanisms not yet fully understood. In this study, we found that the nuclear factor of activated T cell (NFAT) is an unexpected partner of PML: PML specifically enhanced the transcription activation of NFAT. In PML-null mouse embryonic fibroblasts, no transcription activity of NFAT could be detected. There was a selective requirement of PML isoform in NFAT activation: PML-I and PML-VI, but not PML-IV, increased NFAT transactivation. PML specifically promoted the expression of many, but not all, NFAT-targeted genes. We found a specific binding of PML to NFATc. The interaction of PML with NFATc in vivo was further confirmed by chromatin immunoprecipitation and DNA affinity precipitation assay analysis. The unexpected coupling of PML with NFAT reveals a novel mechanism underlying the diverse physiological functions of PML.
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