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Joseph Papamatheakis

Joseph Papamatheakis

IMBB Group Leader (Full Professor Level)
Email address
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Phone
+30-2810-391165
Fax
+30-2810-391101

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.

1: Hadjimichael C, Chanoumidou K, Nikolaou C, Klonizakis A, Theodosi GI, Makatounakis T, Papamatheakis J, Kretsovali A. 
Promyelocytic Leukemia Protein Is an Essential Regulator of Stem Cell Pluripotency and Somatic Cell Reprogramming.
Stem Cell Reports. 2017 May 9;8(5):1366-1378.
PMID: 28392218  [PubMed - indexed for MEDLINE]

2: Sachini N, Papamatheakis J.  
NF-Y and the immune response: Dissecting the complex regulation of MHC genes. 
Biochim Biophys Acta. 2017 May;1860(5):537-542.
PMID: 27989934  [PubMed - indexed for MEDLINE]

3: Favicchio R, Psycharakis S, Schönig K, Bartsch D, Mamalaki C, Papamatheakis J, Ripoll J, Zacharakis G.   
Quantitative performance characterization of three-dimensional noncontact fluorescence molecular tomography. 
J Biomed Opt. 21(2):26009, Feb 2016, doi: 10.1117/1.JBO.21.2.026009.
PMID: 26891600  [PubMed - indexed for MEDLINE]

4: Hadjimichael C, Nikolaou C, Papamatheakis J, Kretsovali A.    
MicroRNAs for Fine-Tuning of Mouse Embryonic Stem Cell Fate Decision through Regulation of TGF-β Signaling.  
Stem Cell Reports. 2016 Mar 8;6(3):292-301.
PMID: 26876669  [PubMed - indexed for MEDLINE]

5: Hadjimichael C, Chanoumidou K, Papadopoulou N, Arampatzi P, Papamatheakis J, Kretsovali A.     
Common stemness regulators of embryonic and cancer stem cells.   
World J Stem Cells. 2015 Oct 26;7(9):1150-84.
PMID: 26516408  [PubMed - indexed for MEDLINE]

6: Hadjimichael C, Chanoumidou K, Papadopoulou N, Arampatzi P, Papamatheakis J, Kretsovali A.     
Promyelocytic Leukemia Protein Is an Essential Regulator of Stem Cell Pluripotency and Somatic Cell Reprogramming.   
Stem Cell Reports. 2017 May 9;8(5):1366-1378.
PMID: 28392218  [PubMed - indexed for MEDLINE]

7: Sachini N, Papamatheakis J.      
NF-Y and the immune response: Dissecting the complex regulation of MHC genes.   
Biochim Biophys Acta. 2017 May;1860(5):537-542.
PMID: 27989934  [PubMed - indexed for MEDLINE]

8: Favicchio R, Psycharakis S, Schönig K, Bartsch D, Mamalaki C, Papamatheakis J, Ripoll J, Zacharakis G.       
Quantitative performance characterization of three-dimensional noncontact fluorescence molecular tomography.   
J Biomed Opt. 2016 Feb;21(2):26009.
PMID: 26891600  [PubMed - indexed for MEDLINE]

9: Hadjimichael C, Nikolaou C, Papamatheakis J, Kretsovali A.        
MicroRNAs for Fine-Tuning of Mouse Embryonic Stem Cell Fate Decision through Regulation of TGF-β Signaling.   
Stem Cell Reports. 2016 Mar 8;6(3):292-301.
PMID: 26876669  [PubMed - indexed for MEDLINE]

10: Hadjimichael C, Chanoumidou K, Papadopoulou N, Arampatzi P, Papamatheakis J, Kretsovali A.         
Common stemness regulators of embryonic and cancer stem cells.    
World J Stem Cells. 2015 Oct 26;7(9):1150-84.
PMID: 26516408  [PubMed - indexed for MEDLINE]

11: Stavride P, Arampatzi P, Papamatheakis J.         
Differential regulation of MHCII genes by PRMT6, via an AT-hook motif of RFX5.    
Mol Immunol. 2013 Dec;56(4):390-8.
PMID: 23911394 [PubMed - indexed for MEDLINE]

12: Papadimitriou L, Zerva I, Georgouli M, Makatounakis T, Papamatheakis J, Athanassakis I.         
DOα⁻β⁺ expression in favor of HLA-DR engagement in exosomes.   
Immunobiology. 2013 Aug;218(8):1019-25.
PMID: 23462321 [PubMed - indexed for MEDLINE]

13: Arampatzi P, Gialitakis M, Makatounakis T, Papamatheakis J.          
Gene-specific factors determine mitotic expression and bookmarking via alternate regulatory elements.    
Nucleic Acids Res. 2013 Feb 1;41(4):2202-15.
PMID: 23303784 [PubMed - indexed for MEDLINE]

14: Karantzali E, Lekakis V, Ioannou M, Hadjimichael C, Papamatheakis J, Kretsovali A.           
Sall1 Regulates Embryonic Stem Cell Differentiation in Association with Nanog.   
J Biol Chem. 2011 Jan 14;286(2):1037-45.
PMID: 21062744 [PubMed - indexed for MEDLINE]

15: Gialitakis M, Arampatzi P, Makatounakis T, Papamatheakis J.           
Gamma Interferon-Dependent Transcriptional Memory via Relocalization of a Gene Locus to PML Nuclear Bodies.   
Mol Cell Biol. 2010 Apr;30(8):2046-56.
PMID: 20123968 [PubMed - indexed for MEDLINE]

16: Garofalakis A, Zacharakis G, Meyer H, Economou EN, Mamalaki C, Papamatheakis J, Kioussis D, Ntziachristos V, Ripoll J.           
Three-dimensional in vivo imaging of green fluorescent protein-expressing T cells in mice with noncontact fluorescence molecular tomography.  
Mol Imaging. 2007 Mar-Apr;6(2):96-107.
PMID: 17445504 [PubMed - indexed for MEDLINE]

17: Gialitakis M, Kretsovali A, Spilianakis C, Kravariti L, Mages J, Hoffmann R, Hatzopoulos AK, Papamatheakis J.           
Coordinated changes of histone modifications and HDAC mobilization regulate the induction of MHC class II genes by Trichostatin A. 
Nucleic Acids Res. 2006 Feb 1;34(3):765-72.
PMID: 16452299 [PubMed - indexed for MEDLINE]

18: Muhlethaler-Mottet A, Krawczyk M, Masternak K, Spilianakis C, Kretsovali A, Papamatheakis J, Reith W.           
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. 2004 Sep 24;279(39):40529-35. 
PMID: 15271997 [PubMed - indexed for MEDLINE]

19: Biel M, Kretsovali A, Karatzali E, Papamatheakis J, Giannis A.
Design, synthesis, and biological evaluation of a small-molecule inhibitor of the histone acetyltransferase Gcn5.
Angew Chem Int Ed Engl. 2004 Jul 26;43(30):3974-6. No abstract available.
PMID: 15274229 [PubMed - indexed for MEDLINE]

20: Muhlethaler-Mottet A, Krawczyk M, Masternak K, Spilianakis C, Kretsovali A, Papamatheakis J, Reith W.
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. 2004 Sep 24;279(39):40529-35. Epub 2004 Jul 22.
PMID: 15271997 [PubMed - indexed for MEDLINE]

21: Spilianakis C, Kretsovali A, Agalioti T, Makatounakis T, Thanos D, Papamatheakis J.
CIITA regulates transcription onset viaSer5-phosphorylation of RNA Pol II.
EMBO J. 2003 Oct 1;22(19):5125-36.
PMID: 14517250 [PubMed - indexed for MEDLINE]

22: Tzortzakaki E, Spilianakis C, Zika E, Kretsovali A, Papamatheakis J.
Steroid receptor coactivator 1 links the steroid and interferon gamma response pathways.
Mol Endocrinol. 2003 Dec;17(12):2509-18. Epub 2003 Aug 21.
PMID: 12933903 [PubMed - indexed for MEDLINE]

23: Karetsou Z, Kretsovali A, Murphy C, Tsolas O, Papamarcaki T.
Prothymosin alpha interacts with the CREB-binding protein and potentiates transcription.
EMBO Rep. 2002 Apr;3(4):361-6. Epub 2002 Mar 15.
PMID: 11897665 [PubMed - indexed for MEDLINE]

24: Kretsovali A, Spilianakis C, Dimakopoulos A, Makatounakis T, Papamatheakis J.
Self-association of class II transactivator correlates with its intracellular localization and transactivation.
J Biol Chem. 2001 Aug 24;276(34):32191-7. Epub 2001 Jun 18.
PMID: 11413136 [PubMed - indexed for MEDLINE]

25: Das S, Lin JH, Papamatheakis J, Sykulev Y, Tsichlis PN.
Differential splicing generates Tvl-1/RFXANK isoforms with different functions.
J Biol Chem. 2002 Nov 22;277(47):45172-80. Epub 2002 Sep 4.
PMID: 12215433 [PubMed - indexed for MEDLINE]

26: Denaxa M, Pavlou O, Tsiotra P, Papadopoulos GC, Liapaki K, Theodorakis K, Papadaki C, Karagogeos D, Papamatheakis J.
The upstream regulatory region of the gene for the human homologue of the adhesion molecule TAG-1 contains elements driving neural specific expression in vivo.
Brain Res Mol Brain Res. 2003 Oct 21;118(1-2):91-101.
PMID: 14559358 [PubMed - indexed for MEDLINE]

27: Spilianakis C, Papamatheakis J, Kretsovali A.
Acetylation by PCAF enhances CIITA nuclear accumulation and transactivation of major histocompatibility complex class II genes.
Mol Cell Biol. 2000 Nov;20(22):8489-98.
PMID: 11046145 [PubMed - indexed for MEDLINE]