The Histone H2B Monoubiquitination Regulatory Pathway Is Required for Differentiation of Multipotent Stem Cells

Oleksandra Karpiuk, Zeynab Najafova, Frank Kramer, Magali Hennion, Christina Galonska, Annekatrin König, Nicolas Snaidero, Tanja Vogel, Andrei Shchebet, Yvonne Begus-Nahrmann, Moustapha Kassem, Mikael Simons, Halyna Shcherbata, Tim Beissbarth, Steven A. Johnsen

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Extensive changes in posttranslational histone modifications accompany the rewiring of the transcriptional program during stem cell differentiation. However, the mechanisms controlling the changes in specific chromatin modifications and their function during differentiation remain only poorly understood. We show that histone H2B monoubiquitination (H2Bub1) significantly increases during differentiation of human mesenchymal stem cells (hMSCs) and various lineage-committed precursor cells and in diverse organisms. Furthermore, the H2B ubiquitin ligase RNF40 is required for the induction of differentiation markers and transcriptional reprogramming of hMSCs. This function is dependent upon CDK9 and the WAC adaptor protein, which are required for H2B monoubiquitination. Finally, we show that RNF40 is required for the resolution of the H3K4me3/H3K27me3 bivalent poised state on lineage-specific genes during the transition from an inactive to an active chromatin conformation. Thus, these data indicate that H2Bub1 is required for maintaining multipotency of hMSCs and plays a central role in controlling stem cell differentiation.

Original languageEnglish (US)
Pages (from-to)705-713
Number of pages9
JournalMolecular Cell
Volume46
Issue number5
DOIs
StatePublished - Jun 8 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Karpiuk, O., Najafova, Z., Kramer, F., Hennion, M., Galonska, C., König, A., Snaidero, N., Vogel, T., Shchebet, A., Begus-Nahrmann, Y., Kassem, M., Simons, M., Shcherbata, H., Beissbarth, T., & Johnsen, S. A. (2012). The Histone H2B Monoubiquitination Regulatory Pathway Is Required for Differentiation of Multipotent Stem Cells. Molecular Cell, 46(5), 705-713. https://doi.org/10.1016/j.molcel.2012.05.022