We study constitutive of signal regulated gene expression. Our aim is to understand cell processes and allow their long term exploitation for the development of useful tools and services. The last few years we have focused on the transcriptional regulation of Major Histocompatibility class II (MHC II) genes that provide a prominent paradigm of a complex gene regulation and protein products transport to the cell membrane where they act as pivotal elements in antigen presentation and immune response. Major contributions are dissecting the properties of CIITA: The interaction of its activation domain with coactivators and PolII kinase, promoter recruitment via the multiprotein complex that binds cooperatively to DNA (enhanceosome), control of its nuclear availability by import/ export that is affected by acetylation and self -association. In the absence of CIITA, epigenetic modification by a Histone Deacetylase inhibitor (DACI) rescues transcription of the MHC locus. Expression profiling identified hundreds of inhibitor targets, including many IFN inducible genes. We showed that IFN α / β itself is induced via a novel mechanism that provides new ways to fight virus infection. Other studies focus on the maintenance of expression states through mitosis. Gene bookmarking is achieved by enhanceosome subunit attachment to the mitotic chromatin. The primary MHC induction generates long term changes manifested by faster and enhanced reinduction. This is a novel mechanism of long term epigenetic memory determined by high promoter Histone dimethylation and locus relocation close to PML (PromoMyelocytic L eukemia) nuclear bodies. Current and future areas to explore include the role of PML in epigenetic control of transcriptional memory and Cancer stem cell biology.

Gialitakis M., P. Arampatzi, T. Makatounakis and J. Papamatheakis (2010) Gamma Interferon dependent transcriptional memory via relocalization of a gene locus to PML nuclear bodies. Mol. Cell. Biol. 30: 2046- 2056.

Garofalakis A, Zacharakis G, Meyer H, Economou EN, Mamalaki C, Papamatheakis J, Kioussis D, Ntziachristos V, Ripoll J. (2007) Three-dimensional in vivo imaging of green fluorescent protein-expressing T cells in mice, with noncontact fluorescence molecular tomography. Mol. Imaging. 6: 96-107.

Gialitakis M, Androniki Kretsovali, Charalampos Spilianakis, Lara Kravariti, Jorg Mages, Reinhard
Hoffmann, Antonis K. Hatzopoulos and Joseph Papamatheakis (2006) Coordinated changes of histone modifications and HDAC mobilization regulate the induction of MHC class II genes by Trichostatin A. Nucleic Acids Research. 34: 765-772.

Muhlethaler-Mottet A, Krawczyk M, Masternak K, Spilianakis C, Kretsovali A, Papamatheakis J, Reith W. (2004) The S Box of Major Histocompatibility Complex Class II Promoters Is a Key Determinant for Recruitment of the Transcriptional Co-activator CIITA. J Biol Chem. 279: 40529-35.

Spilianakis C, Theodora Agalioti, Androniki Kretsovali, Takis Makatounakis Dimitris Thanos, Joseph Papamatheakis (2003) Interferon γ-induced transcription through CIITA-regulated cofactor recruitment and phosphorylation of RNAPII. EMBO J. 19: 5125-5136.