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Mol. Cell. Biol. 30 (8): 2046-2056

Copyright © 2010 by the American Society for Microbiology. All rights reserved.

Gamma Interferon-Dependent Transcriptional Memory via Relocalization of a Gene Locus to PML Nuclear Bodies{triangledown} ,{dagger}

Manolis Gialitakis,1,2 Panagiota Arampatzi,1,2 Takis Makatounakis,1, and Joseph Papamatheakis1,2*

Institute of Molecular Biology and Biotechnology, FORTH, Heraklion 71110, Greece,1 Department of Biology, University of Crete, Heraklion 71110, Greece2

Received for publication 10 July 2009. Revision received 10 September 2009. Accepted for publication 25 January 2010.

Abstract: Memory of past cellular responses is an essential adaptation to repeating environmental stimuli. We addressed the question of whether gamma interferon (IFN-{gamma})-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-{gamma}, 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.

* Corresponding author. Mailing address: Institute of Molecular Biology and Biotechnology, Forth, Heraklion 71110, Greece. Phone: (30) 2810-391165. Fax: (30) 2810-391101. E-mail: papamath{at}

{triangledown} Published ahead of print on 1 February 2010.

{dagger} Supplemental material for this article may be found at

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