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Accueil > Animation scientifique & Evénements > Conférences CICB-Paris > Archives des conférences CICB-Paris de 2015

Role of histone variants in epigenetic phenomena and tumorigenesis

par Marie Körner - publié le , mis à jour le

Ali Hamiche, Chromatine et régulation épigénétique, IGBMC, Strasbourg, France

1octobre, de 11-13h dans la salle R229
The main research activity of our group is to study the role of histone variants and their deposition machineries in the epigenetic control of human genome activity at the genome-wide level. Among the various epigenetic memory mechanisms, the local replacement of canonical histones within the nucleosome by variant histones has the potential to affect considerably the activity of the corresponding genomic regions. Indeed, nucleosomes bearing histone variants have distinct structures and functional activities and some histone variants are incorporated at specific genomic locations. Our laboratory is focusing on the role of histone variants in gene regulation, genome integrity and oncogenesis. We have implicated macroH2A in PARP-1 enzymatic activity and transcription regulation. We have identified and characterized the first vertebrate histone chaperone, involved in the deposition of CENP-A at centromeres. We have also investigated in detail the molecular mechanism of the histone variant H3.3 deposition and found that the death-associated protein DAXX and the chromatin-remodeling factor ATRX are crucial components of the H3.3 deposition machinery. Our data argue that DAXX functions as a histone chaperone involved in the replication-independent deposition of H3.3, thus linking apoptosis to gene regulation. Our finding also provides a clue as to how mutations in in H3.3 and ATRX genes lead to human genetic diseases such as α-thalassemia and cancer. More recently, we have identified ANP32E as a histone chaperone that removes H2AZ from promoters and provided the molecular basis for H2A.Z recognition and H2A.Z/H2B nucleosomal eviction by ANP32E. We have also identified a novel chaperone involved in H2AZ deposition and discovered a novel new link between the histone variant H2AZ and DNA demethylation. Very recently, we have implicated histone variants in cancer initiation and progression. This implication of histone variants in cancer is novel and will certainly help us to understand how the epigenetic information is stored and maintained by histone variants and how its deregulation leads to developmental disorders and cancer.

Mini Biographie d’Ali Hamiche
After receiving a B.S. degree in Biochemistry from the University of Oran (Algeria) in 1990, Ali Hamiche spent the next five years in Dr. Ariel Prunell lab at the University of Paris 6, studying the structure of the nucleosome using biophysical and biochemical methods. He received his Ph.D. in Molecular and Cell Biology in 1995. He was hired by the CNRS in 1996, as a junior Staff Scientist in Helene Richard-Foy lab (Toulouse, France) were he started working on the role of chromatin structure in gene regulation. He continued to focus on chromatin research during his 2 years postdoctoral training with Dr. Carl Wu at NIH (1998-2000), where he discovered the mechanism of chromatin remodeling by the Drosophila NURF complex. In 2003 he joint Annick Harell Bellan Lab at the André Lwoff Institute (IAL) in Villejuif (close to Paris) where he started to develope proteomic techniques to analyze the role of the histone variant macro H2A in gene regulation. In 2008, he was hired as a group leader at IGBMC (Strasbourg, France) where he holds currently a CNRS Director of Research position. His research is devoted to understanding the role of histone variants in epigenetic regulations and tumorigenesis. He has worked extensively on the isolation and purification of histone variant complexes and have studied their role by using the state of the art molecular and cell biology techniques. Among others, Ali Hamiche has isolated and characterized the histone variant CENP-A deposition machineries and identified DAXX as a novel histone chaperone responsible for the replication-independent deposition of H3.3. More recently, his group has identified ANP32E as a histone chaperone that removes H2AZ from promoters and provided the molecular basis for H2A.Z recognition and H2A.Z/H2B nucleosomal eviction by ANP32E. Ali Hamiche work is funded by different French agencies. The team was rated A+ in the evaluation carried out by the AERES committee in 2008 and 2012, and was recently recognized as an outstanding research group (Equipe labelisée) by the National Ligue against Cancer and awarded a five years grant (2014-2019). Recently, Ali Hamiche received the prestigious Dandrimont-Bénicourt price from the French Academia of Sciences for his contribution to the epigenetic field and oncogenesis.

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