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Marcus Buschbeck - MacroH2A contributes to the establishment and stabilization of differentiated epigenomes
Speaker : Marcus Buschbeck - IMPPC, Institute for Predictive and Personalized Medicine of Cancer, Spain
When : thursday 14 th February at 11 am
Where : Salle CO23 (grande salle de réunions du CBP rez-de-chaussée LR6)
Title : MacroH2A contributes to the establishment and stabilization of differentiated epigenomes
The most striking epigenetic alteration occuring on the level of the nucleosome is the complete exchange of a canonical histone H2A for a macroH2A variant. The expression level of macroH2A variants positively correlates with differentiation state of the cell. We have used loss of function approaches in zebrafish emryos, mouse embryonic stem cells and human tissue stem cells to demonstrate that macroH2A contributes to developmental and differentiation processes (1,2). Zebrafish embryos lacking macroH2A display several developmental defects. In mouse ES cells knockdown of macroH2A reduced their capacity to differentiate, best illustrated by a massive expansion of undifferentiated carcinoma tissue in derived teratomas. In the heterogenous culture of primary human keratinocytes macroH2A promoted differentiation and reduced the self-renewal capacity of the pluripotent compartment. Surprisingly in the light of macroH2A being intensively characterized as repressive, we found demonstrate that its pro-differentiation is at least partially dependent on a poorly recognized function favouring transcriptional activation. Novel insight from first high resolution ChIP-seq profiles will be discussed. Finally we will present unpublished results of an exciting researchline developed in collaboration with Dr. Bouvet and the ENS Lyon on the role of macroH2A in tissue regeneration.
Take home message : In line with the recent observation that macroH2A inhibits reprogramming (3) our results substantiate a role for macroH2A in the establishment and maintenance of differentiated epigenomes.
1. Creppe C, Janich P, Cantariño N, Noguera M, Valero V, Musulén E, Douet J, Posavec M, Martín-Caballero J, Sumoy L, Di Croce L, Benitah SA, Buschbeck M. MacroH2A1 regulates the balance between self-renewal and differentiation commitment in embryonic and adult stem cells. Mol Cell Biol (2012).
2. Buschbeck M, Uribesalgo I, Wibowo I, Rué P, Martin D, Gutierrez A, Morey L, Guigó R, López-Schier H, Di Croce L.The histone variant macroH2A is an epigenetic regulator of key developmental genes. Nat Struct Mol Biol (2009).
3. Histone variant macroH2A confers resistance to nuclear reprogramming. Pasque V, Gillich A, Garrett N, Gurdon JB. EMBO J. (2011)
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