Gamma Interferon-Dependent Transcriptional Memory via Relocalization of a Gene Locus to PML Nuclear Bodies

Abstract

Memory of past cellular responses is an essential adaptation to repeating environmental stimuli. We addressed the question of whether gamma interferon (IFN-γ)-inducible transcription generates memory that sensitizes cells to a second stimulus. We have found that the major histocompatibility complex class II gene DRA is relocated to promyelocytic leukemia (PML) nuclear bodies upon induction with IFN-γ, and this topology is maintained long after transcription shut off. Concurrent interaction of PML protein with mixed-lineage leukemia generates a prolonged permissive chromatin state on the DRA gene characterized by high promoter histone H3 K4 dimethylation that facilitates rapid expression upon restimulation. We propose that the primary signal-induced transcription generates spatial and epigenetic memory that is maintained through several cell generations and endows the cell with increased responsiveness to future activation signals.

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This study was supported by a HERAKLEITOS grant from the Hellenic Ministry of Education and intramural IMBB funding.

We thank I. Talianidis and H. de Thé for plasmids, C. Spilianakis for expert technical advice and comments, I. Aifantis and A. Kretsovali for critical comments, and G. Vretzos for excellent technical assistance.