The Histone Variant MacroH2A1.2 Is Necessary for the Activation of Muscle Enhancers and Recruitment of the Transcription Factor Pbx1
Summary: Histone variants complement and integrate histone post-translational modifications in regulating transcription. The histone variant macroH2A1 (mH2A1) is almost three times the size of its canonical H2A counterpart, due to the presence of an ∼25 kDa evolutionarily conserved non-histone macro...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-02-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716000036 |
| _version_ | 1828515022422147072 |
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| author | Stefania Dell’Orso A. Hongjun Wang Han-Yu Shih Kayoko Saso Libera Berghella Gustavo Gutierrez-Cruz Andreas G. Ladurner John J. O’Shea Vittorio Sartorelli Hossein Zare |
| author_facet | Stefania Dell’Orso A. Hongjun Wang Han-Yu Shih Kayoko Saso Libera Berghella Gustavo Gutierrez-Cruz Andreas G. Ladurner John J. O’Shea Vittorio Sartorelli Hossein Zare |
| author_sort | Stefania Dell’Orso |
| collection | DOAJ |
| description | Summary: Histone variants complement and integrate histone post-translational modifications in regulating transcription. The histone variant macroH2A1 (mH2A1) is almost three times the size of its canonical H2A counterpart, due to the presence of an ∼25 kDa evolutionarily conserved non-histone macro domain. Strikingly, mH2A1 can mediate both gene repression and activation. However, the molecular determinants conferring these alternative functions remain elusive. Here, we report that mH2A1.2 is required for the activation of the myogenic gene regulatory network and muscle cell differentiation. H3K27 acetylation at prospective enhancers is exquisitely sensitive to mH2A1.2, indicating a role of mH2A1.2 in imparting enhancer activation. Both H3K27 acetylation and recruitment of the transcription factor Pbx1 at prospective enhancers are regulated by mH2A1.2. Overall, our findings indicate a role of mH2A1.2 in marking regulatory regions for activation. : Dell’Orso et al. report that the histone variant macroH2A1.2 is required for activation of muscle-gene expression and cell differentiation. Genome-wide analyses indicate that macroH2A1.2 is enriched at prospective muscle-specific enhancers where it is required for H3K27 acetylation and recruitment of the transcription factor Pbx1. |
| first_indexed | 2024-12-11T18:07:40Z |
| format | Article |
| id | doaj.art-f10a405ef3944f6d8b32d3ea4d862cdf |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T18:07:40Z |
| publishDate | 2016-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-f10a405ef3944f6d8b32d3ea4d862cdf2022-12-22T00:55:41ZengElsevierCell Reports2211-12472016-02-0114511561168The Histone Variant MacroH2A1.2 Is Necessary for the Activation of Muscle Enhancers and Recruitment of the Transcription Factor Pbx1Stefania Dell’Orso0A. Hongjun Wang1Han-Yu Shih2Kayoko Saso3Libera Berghella4Gustavo Gutierrez-Cruz5Andreas G. Ladurner6John J. O’Shea7Vittorio Sartorelli8Hossein Zare9Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 20892, USALaboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 20892, USALymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, NIAMS, NIH, Bethesda, MD 20892, USALaboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 20892, USAEpigenetics and Regenerative Medicine, IRCCS Fondazione Santa Lucia, 00143 Rome, ItalyLaboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 20892, USAButenandt Institute, LMU Biomedical Center, Department of Physiological Chemistry, Ludwig-Maximilians-University of Munich, 81377 Munich, GermanyLymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, NIAMS, NIH, Bethesda, MD 20892, USALaboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 20892, USA; Corresponding authorLaboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 20892, USASummary: Histone variants complement and integrate histone post-translational modifications in regulating transcription. The histone variant macroH2A1 (mH2A1) is almost three times the size of its canonical H2A counterpart, due to the presence of an ∼25 kDa evolutionarily conserved non-histone macro domain. Strikingly, mH2A1 can mediate both gene repression and activation. However, the molecular determinants conferring these alternative functions remain elusive. Here, we report that mH2A1.2 is required for the activation of the myogenic gene regulatory network and muscle cell differentiation. H3K27 acetylation at prospective enhancers is exquisitely sensitive to mH2A1.2, indicating a role of mH2A1.2 in imparting enhancer activation. Both H3K27 acetylation and recruitment of the transcription factor Pbx1 at prospective enhancers are regulated by mH2A1.2. Overall, our findings indicate a role of mH2A1.2 in marking regulatory regions for activation. : Dell’Orso et al. report that the histone variant macroH2A1.2 is required for activation of muscle-gene expression and cell differentiation. Genome-wide analyses indicate that macroH2A1.2 is enriched at prospective muscle-specific enhancers where it is required for H3K27 acetylation and recruitment of the transcription factor Pbx1.http://www.sciencedirect.com/science/article/pii/S2211124716000036 |
| spellingShingle | Stefania Dell’Orso A. Hongjun Wang Han-Yu Shih Kayoko Saso Libera Berghella Gustavo Gutierrez-Cruz Andreas G. Ladurner John J. O’Shea Vittorio Sartorelli Hossein Zare The Histone Variant MacroH2A1.2 Is Necessary for the Activation of Muscle Enhancers and Recruitment of the Transcription Factor Pbx1 Cell Reports |
| title | The Histone Variant MacroH2A1.2 Is Necessary for the Activation of Muscle Enhancers and Recruitment of the Transcription Factor Pbx1 |
| title_full | The Histone Variant MacroH2A1.2 Is Necessary for the Activation of Muscle Enhancers and Recruitment of the Transcription Factor Pbx1 |
| title_fullStr | The Histone Variant MacroH2A1.2 Is Necessary for the Activation of Muscle Enhancers and Recruitment of the Transcription Factor Pbx1 |
| title_full_unstemmed | The Histone Variant MacroH2A1.2 Is Necessary for the Activation of Muscle Enhancers and Recruitment of the Transcription Factor Pbx1 |
| title_short | The Histone Variant MacroH2A1.2 Is Necessary for the Activation of Muscle Enhancers and Recruitment of the Transcription Factor Pbx1 |
| title_sort | histone variant macroh2a1 2 is necessary for the activation of muscle enhancers and recruitment of the transcription factor pbx1 |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716000036 |
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