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RNA-sequencing of C3H/10T1/2 mesenchymal stem cells expressing H2B mutant histones

ABSTRACT: Purpose of study is to assess changes in gene expression profiles of mesenchymal stem cell upon expression of H2BE71K/Q, H2BE76K/Q and H2BE113K/Q

ORGANISM(S): Mus musculus

PROVIDER: GSE146959 | GEO | 2020/11/11

REPOSITORIES: GEO

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RNA-sequencing of C3H/10T1/2 mesenchymal stem cells expressing H2B mutant histones

Project description:RNA-sequencing of C3H/10T1/2 mesenchymal stem cells expressing H2B mutant histones

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Selvaggio2020 - Microenvironment control of hybrid Epithelial-Mesenchymal phenotypes

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Protein expression profiles of C3H 10T1/2 murine fibroblasts and of isogenic cells transformed by the H1047R mutant of phosphoinositide 3-kinase (PI3K).

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Project description:Monoubiquitination is a major histone post-translational modification. In humans, the histone H2B K120 and histone H4 K31 residues are monoubiquitinated and may form transcriptionally active chromatin. In this study, we reconstituted nucleosomes containing H2B monoubiquitinated at position 120 (H2Bub120) and/or H4 monoubiquitinated at position 31 (H4ub31). We found that the H2Bub120 and H4ub31 monoubiquitinations differently affect nucleosome stability: the H2Bub120 monoubiquitination enhances the H2A-H2B association with the nucleosome, while the H4ub31 monoubiquitination decreases the H3-H4 stability in the nucleosome, when compared with the unmodified nucleosome. The H2Bub120 and H4ub31 monoubiquitinations both antagonize the Mg(2+)-dependent compaction of a poly-nucleosome, suggesting that these monoubiquitinations maintain more relaxed conformations of chromatin. In the crystal structure, the H2Bub120 and H4ub31 monoubiquitinations do not change the structure of the nucleosome core particle and the ubiquitin molecules were flexibly disordered in the H2Bub120/H4ub31 nucleosome structure. These results revealed the differences and similarities of the H2Bub120 and H4ub31 monoubiquitinations at the mono- and poly-nucleosome levels and provide novel information to clarify the roles of monoubiquitination in chromatin.

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