Functional genomics of normal and leukemic T cells
Mobile: +33 (0)6 99 02 48 41
Phone: +33 (0)4 91 82 87 17
Salvatore Spicuglia (CR1)
Eve-Lyne Mathieu (post-doc)
Jaafar Aliomari (PhD student)
Saadat Hussain (PhD student)
Alexander España (PhD student)
Wilson Goma (Engineer)
Wiam Saadi (Master M2)
Yasmina Kermezli (Master M2)
Denis Puthier (Maitre de conférences)
Lydie Pradel (Maitre de conférences)
Past Students & Post-docs
Ariel Galindo (post-doc)
Laurent Vanhille (post-doc)
Aurélien Griffon (PhD student)
Dao Thi Mai Lan (PhD student)
Mohamed Belhocine (PhD student)
Marc Antoine Garibal (M2 Student)
Zhonglin Li (M2 Student)
Charbel Souaid (M2 Student)
The Spicuglia’s group is focused on the characterization of the mouse and human epigenomes during the differentiation of T cells and in leukemia. We aim to address how the epigenetic marks are governing the way in which genomic information is organized within the cell and how these phenomena play a role in regulating gene expression and in controlling specific cellular functions during cell differentiation and cancer.
Our team has a long-standing interest in the fields of epigenetics and transcriptional regulation during lymphoid cell differentiation. We have set up and developed up-to-date genome-wide investigating approaches (MeDIP, ChIP-seq, FAIRE-seq, MNase-seq and RNA-seq), along with state-of-the-art bioinformatics, in order to study epigenetics together with transcriptional regulation in normal developing and transformed T lymphocytes. In the past years, we have explored the dynamics of selected histone modifications and transcription factors during early T cell development in vivo, using ChIP assays coupled to either microarrays or HTS technologies. Our data evidenced a previously unappreciated combinatorial of histone methylations associated to the activity of developmentally regulated enhancers. and highlighted an epigenetic signature linked to the regulation of tissue specific gene expression, suggesting a direct connection between chromatin landscapes and distinct modes of transcriptional regulation. In parallel, we have made significant effort in implementing collaborative projects with clinicians, aiming to apply these techniques to the definition of epigenetic signatures (both DNA methylation and histone modifications) in large collections of human lymphoma and leukemia primary cell samples.
1. Chromatin dynamics in developing T-cells using genome-wide approaches
2. Control of tissue-specific gene expression in normal and leukemic T cells
3. Epigenetic characterization of cancer cells using genome-wide approaches
1. Galindo-Albarrán A., O. López-Portales, D. Gutiérrez-Reyna, O Rodríguez-Jorge, J Sánchez-Villanueva, O Ramírez-Pliego, A Bergon, B Loriod, H Holota, J Imbert, A Hernández-Mendoza, P Ferrier, E Carrillo-de Santa Pau, A Valencia, S Spicuglia*, M.A. Santana*. CD8+ T cells from human neonates are biased towards innate immunity.Cell reports. Nov 15;17(8):2151-2160. PMID: 27851975. *co-corresponding authors
2. Cauchy P, Maqbool M, Zacarias-Cabeza J, Vanhille L, Koch F, Fenouil R, Gut M, Gut I, Santana M, Griffon A, Imbert J, Moraes-Cabé C, Bories JC, Ferrier P, Spicuglia S*, Andrau JC*(2015). Dynamic recruitment of Ets1 to both nucleosome -occupied and -depleted enhancer regions mediates a transcriptional program switch during early T-cell differentiation. Nucleic Acids Res. 2015 Dec 15. PMID: 26673693. *corresponding authors
3. Vanhille L., A. Griffon, M.A. Maqbool, J. Zacarias, L.T.M. Dao, N. Fernandez, B. Ballester, J.C. Andrau, S. Spicuglia (2015). CapStarr-seq: a high-throughput method for quantitative assessment of enhancer activity in mammals. Nat. Comm. 6:6905.
4. J. Zacarías-Cabeza, M. Belhocine, L. Vanhille, P. Cauchy, F. Koch, A. Pekowska, R. Fenouil, A. Bergon, M. Gut, I. Gut, D. Eick, J. Imbert, P. Ferrier, J.C. Andrau and S. Spicuglia (2015). Transcription dependent generation of a specialized chromatin structure at the TCRblocus. J. Immunol. 194(7):3432-43.
5. Lepoivre C, Belhocine M, Bergon A, Griffon A, Yammine M, Vanhille L, Zacarias-Cabeza J, Garibal M.A., Koch F, Maqbool M, Fenouil R, Loriod B, Holota H, Gut M, Gut I, Imbert J, Andrau J.C., Puthier D, Spicuglia S (2013). Divergent transcription is associated with promoters of transcriptional regulators. BMC Genomics. Dec 23,14(1):914.
6. Pekowska A, Benoukraf T, Zacarias-Cabeza J, Belhocine M, Koch F, Holota H, Imbert J, Andrau J.C, Ferrier P and Spicuglia S (2011). H3K4 tri-methylation provides an epigenetic signature of active enhancers. EMBO J., 30, 4198–10.
7. Pekowska A, Benoukraf T, Ferrier P and Spicuglia S (2010) A unique H3K4me2 profile marks tissue-specific gene regulation. Genome Research. 20(11):1493-502.
8. Bonnet, M., Huang, F., Benoukraf, T., Cabaud, O., Verthuy, C., Boucher, A., Jaeger, S., Ferrier, P., and Spicuglia, S. (2009). Duality of enhancer functioning mode revealed in a reduced TCRbeta gene enhancer knockin mouse model. J Immunol183, 7939-7948.
Last update: 17 February 2012