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Gamma Interferon-Dependent Transcriptional Memory via Relocalization of a Gene Locus to PML Nuclear Bodies,
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 adaptationto repeating environmental stimuli. We addressed the questionof whether gamma interferon (IFN-)-inducible transcription generatesmemory that sensitizes cells to a second stimulus. We have foundthat the major histocompatibility complex class II gene DRAis relocated to promyelocytic leukemia (PML) nuclear bodiesupon induction with IFN-, and this topology is maintained longafter transcription shut off. Concurrent interaction of PMLprotein with mixed-lineage leukemia generates a prolonged permissivechromatin state on the DRA gene characterized by high promoterhistone H3 K4 dimethylation that facilitates rapid expressionupon restimulation. We propose that the primary signal-inducedtranscription generates spatial and epigenetic memory that ismaintained through several cell generations and endows the cellwith 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}imbb.forth.gr
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)-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-
Published ahead of print on 1 February 2010. 
Supplemental material for this article may be found at 
