Regulation of gene expression can be accomplished "in cis" by several regulatory elements exerting their action on physically linked genes on the same chromosome. A "trans" regulation aspect of gene expression has also recently been brought to light by studies of the interactions and function of regulatory elements located on a chromosome different from the one that carries the regulated gene. Such regulatory elements include enhancers or locus control regions that are shown to be able to regulate the expression not only of cis linked genes but also of genes located on different chromosomes, in trans .
The main objective of our laboratory is to apply a combination of biocomputing, molecular, biochemical, imaging and genetic approaches in order to identify and characterize protein complexes that generate and/or maintain long range chromosomal interactions in cell populations of the innate and adaptive immune system. We aim to provide substantial information on how the genome is shaped as a whole and how the nuclear structure patterns in the context of distinct subnuclear microenvironments regulate global gene expression (3D epigenetics).
Williams A, Lee GR, Spilianakis CG, Hwang SS, Eisenbarth SC, Flavell RA. (2013) Hypersensitive site 6 of the Th2 locus control region is essential for Th2 cytokine expression. Proc Natl Acad Sci U S A. 110:6955-6960.
Deligianni C, Spilianakis C. (2012) Long-range genomic interactions epigenetically regulate the expression of a cytokine receptor. EMBO Reports 13:819-826.
Spilianakis CG, Lalioti M, Town T, Lee GR, Flavell RA. (2005) Interchromosomal associations between alternatively expressed loci. Nature 435:637-645.
Lee GR, Spilianakis CG, Flavell RA. (2005) Hypersensitive site 7 of the TH2 locus control region is essential for expressing TH2 cytokine genes and for long-range intrachromosomal interactions. Nat Immunol. 6:42-8.
Spilianakis CG, Flavell RA. (2004) Long-range intrachromosomal interactions in the T helper type 2 cytokine locus. Nat Immunol. 5:1017-27.
Doxaki C, Kampranis SC, Eliopoulos AG, Spilianakis C, Tsatsanis C. Coordinated Regulation of miR-155 and miR-146a Genes during Induction of Endotoxin Tolerance in Macrophages. J Immunol. 2015, 195: 5750-5761
Stratigi K., Kapsetaki M., Aivaliotis M., Town T., Flavell RA., Spilianakis CG. Spatial proximity of homologous alleles and long noncoding RNAs regulate a switch in allelic gene expression. Proc Natl Acad Sci U S A., 2015, 112:E1577-1586
Zorca CE, Kim LK, Kim YJ, Krause MR, Zenklusen D, Spilianakis CG, Flavell RA. Myosin VI regulates gene pairing and transcriptional pause release in T cells. Proc Natl Acad Sci U S A., 2015, 112:E1587-1593
Williams A., Lee G.R., Spilianakis C.G., Hwang S.S., Eisenbarth S.C., Flavell R.A. Hypersensitive site 6 of the Th2 locus control region is essential for Th2 cytokine expression. Proc Natl Acad Sci U S A., 2013, 110: 6955-6960.
Deligianni C, Spilianakis C. Long-range genomic interactions epigenetically regulate the expression of a cytokine receptor. EMBO Reports, 2012, doi:10.1038/embor.2012.112.
Ktistaki E, Garefalaki A, Williams A, Andrews SR, Bell DM, Foster KE, Spilianakis CG, Flavell RA, Kosyakova N, Trifonov V, Liehr T, Kioussis D. CD8 locus nuclear dynamics during thymocyte development. J Immunol. 2010, 184(10):5686-95.
Williams A, Spilianakis CG, Flavell RA. Interchromosomal association and gene regulation in trans. Trends Genet. 2010, 26(4):188-97.
Deligianni C, Spilianakis C.G. Long range genomic cytokine-receptor interaction regulates gene expression. Cytokine 2009;48: 1-2, Sp. Iss. SI Pages: 2-2.
Spilianakis C.G. Interchromosomal cytokine gene regulation. Cytokine 2009; 48: 1-2, Sp. Iss. SI Pages: 3-3.
Amsen D, Spilianakis CG, Flavell RA. How are T(H)1 and T(H)2 effector cells made? Curr. Opin.Immunol. 2009, 2: 153-60.
Brown MR, Kronengold J, Gazula VR, Spilianakis CG, Flavell RA, von Hehn CA, Bhattacharjee A, Kaczmarek LK. Amino-termini isoforms of the Slack K+ channel, regulated by alternative promoters, differentially modulate rhythmic firing and adaptation. J Physiol. 2008 , 586(Pt 21):5161-79.
Town T, Breunig JJ, Sarkisian MR, Spilianakis CG, Ayoub AE, Liu X, Ferrandino AF, Gallagher AR, Li MO, Rakic P, Flavell RA. The stumpy gene is required for mammalian ciliogenesis. Proc Natl Acad Sci U S A. 2008, 105(8):2853-8.
Spilianakis C.G., Flavell R.A. Molecular biology. Managing associations between different chromosomes. Science. 2006, 312:207-8.
Lee G.R., Kim S.T., Spilianakis C.G., Fields P.E., Flavell R.A. T helper cell differentiation: Regulation by cis-elements and epigenetics. Immunity .2006,4:369-79.
Gialitakis M., Kretsovali A., Spilianakis C.G. , Kravariti, L., Mages J., Hoffmann R., Hatzopoulos A.K., 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, 34:765-72.
Spilianakis C.G. , Lee G.R., Flavell R.A. Twisting the Th1/Th2 immune response via the retinoid X receptor: Lessons from a genetic approach. Eur J Immunol. 2005, 35:3400-4.
Spilianakis C.G., Lalioti M., Town T., et al. Epigenetic regulation of cytokine gene expression. Immunology 2006, 116: 30-30 Supplement: Suppl. 1
Spilianakis C.G., Lalioti M., Town T., Lee GR., Flavell RA. Interchromosomal associations between alternatively expressed loci. Nature (Research Article). 2005, 435:637-645.
Lee GR, Spilianakis C.G., Flavell RA. Hypersensitive site 7 of the TH2 locus control region is essential for expressing TH2 cytokine genes and for long-range intrachromosomal interactions. Nat Immunol. 2005, 6:42-8.
Spilianakis C.G., Flavell RA. Long-range intrachromosomal interactions in the T helper type 2 cytokine locus. Nat Immunol. 2004, 5:1017-27.
Muhlethaler-Mottet A., Krawczyk M., Masternak K., Spilianakis C.G. , 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, 279:40529-35.
Spilianakis C.G., Kretsovali A., Agalioti T., Makatounakis T., Thanos D., Papamatheakis J. CIITA regulates transcription onset viaSer5-phosphorylation of RNA Pol II. EMBO J. 2003, 22:5125-36.
Tzortzakaki E., Spilianakis C.G., Zika E., Kretsovali A., Papamatheakis J. Steroid receptor coactivator 1 links the steroid and interferon gamma response pathways. Mol Endocrinol. 2003, 12:2509-18.
Spilianakis C.G., Kretsovali A., Dimakopoulos A., Makatounakis T., Papamatheakis J. Self-association of class II transactivator correlates with its intracellular localization and transactivation. J Biol Chem. 2001, 276:32191-7.
Spilianakis C.G , Papamatheakis J, Kretsovali A. Acetylation by PCAF enhances CIITA nuclear accumulation and transactivation of major histocompatibility complex class II genes. Mol Cell Biol. 2000, 20:8489-98.
Kretsovali A., Agalioti T., Spilianakis C.G., Tzortzakaki E., Merika M., Papamatheakis J. Involvement of CREB binding protein in expression of major histocompatibility complex class II genes via interaction with the class II transactivator. Mol Cell Biol. 1998, 18:6777-83.