Transcription and Epigenomics in developing T-cells

 Jean-Christophe ANDRAU

 IGMM - UMR 5535

 1919 route de Mende, 34293 Montpellier

Phone: +33 4 34 35 96 52

Email: jean-christophe.andrau@igmm.cnrs.fr

Website

During differentiation, important epigenetic and transcriptional changes occur to allow stem cells to modulate expression of their original genetic program, resulting in dramatic transitions in cellular functions and properties. Enhancers and promoters of both coding and noncoding genes are major genomic modules, crucial for regulating this process. Our team is interested in the process of transcription and epigenetic control of mammalian cells with a specific focus on T cell differentiation. We develop 3 main research axes centered on chromatin and transcription biology, using genome-wide approaches.

In our first axis, we study the role of the Carboxy-Terminal Domain of RNA Polymerase II in transcriptional regulation. This domain is central to many processes linked to transcription and RNA processing and we have recently showed that it plays a major role in transcription termination control at both ends of the genes. We try now to get further insights into the role of this domain and of RNA polymerase II in 3D genome organization. In our second axis, we investigate why genes are using multiple enhancers in a dynamic manner to regulate their expression. In our third axis, we develop tools and analyses decipher the rules of promoter opening and their consequences gene activation. For more information, visit our website.

Keywords: Transcription, Chromatin, Enhancers, promoters, Genomics, T-cell differentiation.

Main publications :

• Tyrosine-1 of RNA Polymerase II CTD controls global termination of gene transcription in mammals. Shah N**, Maqbool MA**, Yahia Y, Zine El Aabidine A, Esnault C, Fonré I, Decker TM, Martin D, Schuller R, Krebs S, Blum H, Ihmof A, Eick D*, Andrau JC* Molecular Cell 2018 Jan 4;69(1):48-61.e6. doi: 10.1016/j.molcel.2017.12.009. PMID: 29304333.
• Two possible modes of pioneering associated with combinations of H2A.Z and p300/CBP at nucleosome-occupied enhancers.” Cauchy, P., F. Koch and J. C. Andrau* (2017). Transcription Feb 13:e1291395. PMID: 28301306..
• Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells. Soucie, E. L., Z. Weng, L. Geirsdottir, K. Molawi, J. Maurizio, R. Fenouil, N. Mossadegh-Keller, G. Gimenez, L. VanHille, M. Beniazza, J. Favret, C. Berruyer, P. Perrin, N. Hacohen, J. C. Andrau, P. Ferrier, P. Dubreuil, A. Sidow and M. H. Sieweke (2016). Science 351(6274): aad5510. PMID: 26797145.
• Dynamic recruitment of Ets1 to both nucleosome-occupied and -depleted enhancer regions mediates a transcriptional program switch during early T-cell differentiation. Cauchy, P., M. A. Maqbool, J. Zacarias-Cabeza, L. Vanhille, F. Koch, R. Fenouil, M. Gut, I. Gut, M. A. Santana, A. Griffon, J. Imbert, C. Moraes-Cabe, J. C. Bories, P. Ferrier, S. Spicuglia* and J. C. Andrau * (2016). Nucleic Acids Res 44(8): 3567-3585. PMID: 26673693.
• Site- and allele-specific polycomb dysregulation in T-cell leukaemia. Navarro, J. M., A. Touzart, L. C. Pradel, M. Loosveld, M. Koubi, R. Fenouil, S. Le Noir, M. A. Maqbool, E. Morgado, C. Gregoire, S. Jaeger, E. Mamessier, C. Pignon, S. Hacein-Bey-Abina, B. Malissen, M. Gut, I. G. Gut, H. Dombret, E. A. Macintyre, S. J. Howe, H. B. Gaspar, A. J. Thrasher, N. Ifrah, D. Payet-Bornet, E. Duprez**, J. C. Andrau**, V. Asnafi **and B. Nadel **(2015). Nat Commun 6: 6094. PMID: 25615415.
• High-throughput and quantitative assessment of enhancer activity in mammals by CapStarr-seq. Vanhille, L., A. Griffon, M. A. Maqbool, J. Zacarias-Cabeza, L. T. Dao, N. Fernandez, B. Ballester, J. C. Andrau and S. Spicuglia (2015). Nat Commun 6: 6905. PMID: 25872643.
• Tyrosine phosphorylation of RNA polymerase II CTD is associated with antisense promoter transcription and active enhancers in mammalian cells. Descostes, N.**, M. Heidemann, L.** Spinelli, R. Schuller, M. A. Maqbool, R. Fenouil, F. Koch, C. Innocenti, M. Gut, I. Gut, D. Eick *and J. C. Andrau* (2014). Elife 3: e02105. PMID: 24842994.
• CpG islands and GC content dictate nucleosome depletion in a transcription-independent manner at mammalian promoters. Fenouil R**, Cauchy P**, Koch F**, Descostes N, Cabeza JZ, Innocenti C, Ferrier P, Spicuglia S, Gut M, Gut I, Andrau JC* (2012). Genome Res  22, 2399-2408. PMID: 23100115.
• Noncoding transcription at enhancers: general principles and functional models. Natoli G*, and Andrau JC* (2012). Annu Rev Genet 46, 1-19. PMID:22905871.
• Transcription initiation platforms and GTF recruitment at tissue-specific enhancers and promoters. Koch F, Fenouil R, Gut M, Cauchy P, Albert TK, Zacarias-Cabeza J, Spicuglia S, de la Chapelle AL, Heidemann M, Hintermair C, Eick D, Gut I, Ferrier P*, Andrau JC* (2011). Nat Struct Mol Biol. 17;18(8):956-63. PMID: 21765417.