Structural Basis for EPC1-Mediated Recruitment of MBTD1 into the NuA4/TIP60 Acetyltransferase Complex
Summary: MBTD1, a H4K20me reader, has recently been identified as a component of the NuA4/TIP60 acetyltransferase complex, regulating gene expression and DNA repair. NuA4/TIP60 inhibits 53BP1 binding to chromatin through recognition of the H4K20me mark by MBTD1 and acetylation of H2AK15, blocking th...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720303016 |
| _version_ | 1818912627471941632 |
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| author | Heng Zhang Maëva Devoucoux Xiaosheng Song Li Li Gamze Ayaz Harry Cheng Wolfram Tempel Cheng Dong Peter Loppnau Jacques Côté Jinrong Min |
| author_facet | Heng Zhang Maëva Devoucoux Xiaosheng Song Li Li Gamze Ayaz Harry Cheng Wolfram Tempel Cheng Dong Peter Loppnau Jacques Côté Jinrong Min |
| author_sort | Heng Zhang |
| collection | DOAJ |
| description | Summary: MBTD1, a H4K20me reader, has recently been identified as a component of the NuA4/TIP60 acetyltransferase complex, regulating gene expression and DNA repair. NuA4/TIP60 inhibits 53BP1 binding to chromatin through recognition of the H4K20me mark by MBTD1 and acetylation of H2AK15, blocking the ubiquitination mark required for 53BP1 localization at DNA breaks. The NuA4/TIP60 non-catalytic subunit EPC1 enlists MBTD1 into the complex, but the detailed molecular mechanism remains incompletely explored. Here, we present the crystal structure of the MBTD1-EPC1 complex, revealing a hydrophobic C-terminal fragment of EPC1 engaging the MBT repeats of MBTD1 in a site distinct from the H4K20me binding site. Different cellular assays validate the physiological significance of the key residues involved in the MBTD1-EPC1 interaction. Our study provides a structural framework for understanding the mechanism by which MBTD1 recruits the NuA4/TIP60 acetyltransferase complex to influence transcription and DNA repair pathway choice. : EPC1 is a critical component of the NuA4/TIP60 acetyltransferase complex involved in gene expression and genome maintenance. Zhang et al. illuminate the structural and molecular basis for EPC1 bound to the H4K20me reader MBTD1, highlighting the important role of their association in gene transcription and DNA repair. Keywords: MBTD1, EPC1, NuA4, TIP60, H4K20me, DNA repair, crystal structure |
| first_indexed | 2024-12-19T23:17:36Z |
| format | Article |
| id | doaj.art-05faa42449cc456aaa9a4be6a091f859 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-19T23:17:36Z |
| publishDate | 2020-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-05faa42449cc456aaa9a4be6a091f8592022-12-21T20:02:03ZengElsevierCell Reports2211-12472020-03-01301239964002.e4Structural Basis for EPC1-Mediated Recruitment of MBTD1 into the NuA4/TIP60 Acetyltransferase ComplexHeng Zhang0Maëva Devoucoux1Xiaosheng Song2Li Li3Gamze Ayaz4Harry Cheng5Wolfram Tempel6Cheng Dong7Peter Loppnau8Jacques Côté9Jinrong Min10Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, CanadaSt. Patrick Research Group in Basic Oncology, Laval University Cancer Research Center, Oncology division of CHU de Québec-Université Laval Research Center, Quebec City, QC G1R 3S3, CanadaStructural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, CanadaStructural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, CanadaStructural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Biology, Middle East Technical University, Ankara, TurkeyStructural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, CanadaStructural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, CanadaStructural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, CanadaStructural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, CanadaSt. Patrick Research Group in Basic Oncology, Laval University Cancer Research Center, Oncology division of CHU de Québec-Université Laval Research Center, Quebec City, QC G1R 3S3, Canada; Corresponding authorHubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, PR China; Structural Genomics Consortium and Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Corresponding authorSummary: MBTD1, a H4K20me reader, has recently been identified as a component of the NuA4/TIP60 acetyltransferase complex, regulating gene expression and DNA repair. NuA4/TIP60 inhibits 53BP1 binding to chromatin through recognition of the H4K20me mark by MBTD1 and acetylation of H2AK15, blocking the ubiquitination mark required for 53BP1 localization at DNA breaks. The NuA4/TIP60 non-catalytic subunit EPC1 enlists MBTD1 into the complex, but the detailed molecular mechanism remains incompletely explored. Here, we present the crystal structure of the MBTD1-EPC1 complex, revealing a hydrophobic C-terminal fragment of EPC1 engaging the MBT repeats of MBTD1 in a site distinct from the H4K20me binding site. Different cellular assays validate the physiological significance of the key residues involved in the MBTD1-EPC1 interaction. Our study provides a structural framework for understanding the mechanism by which MBTD1 recruits the NuA4/TIP60 acetyltransferase complex to influence transcription and DNA repair pathway choice. : EPC1 is a critical component of the NuA4/TIP60 acetyltransferase complex involved in gene expression and genome maintenance. Zhang et al. illuminate the structural and molecular basis for EPC1 bound to the H4K20me reader MBTD1, highlighting the important role of their association in gene transcription and DNA repair. Keywords: MBTD1, EPC1, NuA4, TIP60, H4K20me, DNA repair, crystal structurehttp://www.sciencedirect.com/science/article/pii/S2211124720303016 |
| spellingShingle | Heng Zhang Maëva Devoucoux Xiaosheng Song Li Li Gamze Ayaz Harry Cheng Wolfram Tempel Cheng Dong Peter Loppnau Jacques Côté Jinrong Min Structural Basis for EPC1-Mediated Recruitment of MBTD1 into the NuA4/TIP60 Acetyltransferase Complex Cell Reports |
| title | Structural Basis for EPC1-Mediated Recruitment of MBTD1 into the NuA4/TIP60 Acetyltransferase Complex |
| title_full | Structural Basis for EPC1-Mediated Recruitment of MBTD1 into the NuA4/TIP60 Acetyltransferase Complex |
| title_fullStr | Structural Basis for EPC1-Mediated Recruitment of MBTD1 into the NuA4/TIP60 Acetyltransferase Complex |
| title_full_unstemmed | Structural Basis for EPC1-Mediated Recruitment of MBTD1 into the NuA4/TIP60 Acetyltransferase Complex |
| title_short | Structural Basis for EPC1-Mediated Recruitment of MBTD1 into the NuA4/TIP60 Acetyltransferase Complex |
| title_sort | structural basis for epc1 mediated recruitment of mbtd1 into the nua4 tip60 acetyltransferase complex |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720303016 |
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