Speaker: Marcus Buschbeck,
Chromatin and Cell Fate Laboratory, The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Badalona, Spain.

Organizer: Oncology Programme
Host: Eduard Batlle, IRB Barcelona
Date: Thursday, 17 November 2011, 12:00h.
Place: Sala Fèlix Serratosa, Parc Cièntific de Barcelona, Spain

ABSTRACT:
Among all histone variants macroH2A differs most from its canonical counterpart. But what is the function of this unique and facultative nucleosome component?
From our earlier studies we knew that in human pluripotent cells macroH2A is bound to promoters of key developmental genes [1]. MacroH2A was required for correct differentiation and loss-of-function in vivo induced severe developmental defects in zebrafish embryos. We speculated that in embryonic stem cells macroH2A might be essential for proper lineage commitment [2]. We now provide first insight in the function of this unique histone variant in embryonic and adult stem cells. We show that knockdown of macroH2A1 does not affect selfrenewal of embryonic stem cells but limits their capacity to differentiate [3]. Loss of macroH2A1 interferes with proper inactivation of pluripotency genes and results in a reduction and/or delay in the activation of differentiation genes most of which are direct target genes of macroH2A. In addition MacroH2A1-deficient mES cells form defective embryoid bodies that are reduced in size and lack stage-specific cavitation. The requirement of macroH2A1 for proper differentiation is further illustrated in vivo by the massive expansion of immature tissue in macroH2A1-deficient teratomas. Furthermore, in the heterogeneous culture of primary human keratinocytes macroH2A1 levels negatively affect the self-renewal capacity of the pluripotent compartment. Taken together these results identify macroH2A1 as a critical chromatin component regulating the delicate balance between self-renewal and differentiation of embryonic and adult stem cells.
[1] Buschbeck et al., Nature Struct Mol Biol (2009)
[2] Buschbeck and Di Croce, Epigenetics (2010)
[3] Creppe et al., submitted (2011)