The histone H2B monoubiquitination regulatory pathway is required for differentiation of multipotent stem cells.
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The histone H2B monoubiquitination regulatory pathway is required for differentiation of multipotent stem cells. / Karpiuk, Oleksandra; Najafova, Zeynab; Kramer, Frank; Hennion, Magali; Galonska, Christina; König, Annekatrin; Snaidero, Nicolas; Vogel, Tanja; Shchebet, Andrei; Begus-Nahrmann, Yvonne; Kassem, Moustapha; Simons, Mikael; Shcherbata, Halyna; Beissbarth, Tim; Johnsen, Steven A.
In: MOL CELL, Vol. 46, No. 5, 5, 2012, p. 705-713.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The histone H2B monoubiquitination regulatory pathway is required for differentiation of multipotent stem cells.
AU - Karpiuk, Oleksandra
AU - Najafova, Zeynab
AU - Kramer, Frank
AU - Hennion, Magali
AU - Galonska, Christina
AU - König, Annekatrin
AU - Snaidero, Nicolas
AU - Vogel, Tanja
AU - Shchebet, Andrei
AU - Begus-Nahrmann, Yvonne
AU - Kassem, Moustapha
AU - Simons, Mikael
AU - Shcherbata, Halyna
AU - Beissbarth, Tim
AU - Johnsen, Steven A.
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Humans
KW - Protein Processing, Post-Translational
KW - Cell Line
KW - Ubiquitination
KW - Histones/metabolism
KW - Mesenchymal Stromal Cells/cytology/metabolism
KW - Adaptor Proteins, Signal Transducing/genetics/physiology
KW - Cell Differentiation/genetics
KW - Chromatin Assembly and Disassembly
KW - Cyclin-Dependent Kinase 9/genetics/physiology
KW - Multipotent Stem Cells/cytology/metabolism
KW - Ubiquitin-Protein Ligases/genetics/metabolism/physiology
KW - Humans
KW - Protein Processing, Post-Translational
KW - Cell Line
KW - Ubiquitination
KW - Histones/metabolism
KW - Mesenchymal Stromal Cells/cytology/metabolism
KW - Adaptor Proteins, Signal Transducing/genetics/physiology
KW - Cell Differentiation/genetics
KW - Chromatin Assembly and Disassembly
KW - Cyclin-Dependent Kinase 9/genetics/physiology
KW - Multipotent Stem Cells/cytology/metabolism
KW - Ubiquitin-Protein Ligases/genetics/metabolism/physiology
M3 - SCORING: Journal article
VL - 46
SP - 705
EP - 713
JO - MOL CELL
JF - MOL CELL
SN - 1097-2765
IS - 5
M1 - 5
ER -