The structure of the core NuRD repression complex provides insights into its interaction with chromatin
The NuRD complex is a multi-protein transcriptional corepressor that couples histone deacetylase and ATP-dependent chromatin remodelling activities. The complex regulates the higher-order structure of chromatin, and has important roles in the regulation of gene expression, DNA damage repair and cell...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/13941 |
| _version_ | 1811236934143442944 |
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| author | Christopher J Millard Niranjan Varma Almutasem Saleh Kyle Morris Peter J Watson Andrew R Bottrill Louise Fairall Corinne J Smith John WR Schwabe |
| author_facet | Christopher J Millard Niranjan Varma Almutasem Saleh Kyle Morris Peter J Watson Andrew R Bottrill Louise Fairall Corinne J Smith John WR Schwabe |
| author_sort | Christopher J Millard |
| collection | DOAJ |
| description | The NuRD complex is a multi-protein transcriptional corepressor that couples histone deacetylase and ATP-dependent chromatin remodelling activities. The complex regulates the higher-order structure of chromatin, and has important roles in the regulation of gene expression, DNA damage repair and cell differentiation. HDACs 1 and 2 are recruited by the MTA1 corepressor to form the catalytic core of the complex. The histone chaperone protein RBBP4, has previously been shown to bind to the carboxy-terminal tail of MTA1. We show that MTA1 recruits a second copy of RBBP4. The crystal structure reveals an extensive interface between MTA1 and RBBP4. An EM structure, supported by SAXS and crosslinking, reveals the architecture of the dimeric HDAC1:MTA1:RBBP4 assembly which forms the core of the NuRD complex. We find evidence that in this complex RBBP4 mediates interaction with histone H3 tails, but not histone H4, suggesting a mechanism for recruitment of the NuRD complex to chromatin. |
| first_indexed | 2024-04-12T12:17:41Z |
| format | Article |
| id | doaj.art-4ec4f0e5e4d146ce9e4fdf503a7b8149 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:17:41Z |
| publishDate | 2016-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4ec4f0e5e4d146ce9e4fdf503a7b81492022-12-22T03:33:23ZengeLife Sciences Publications LtdeLife2050-084X2016-04-01510.7554/eLife.13941The structure of the core NuRD repression complex provides insights into its interaction with chromatinChristopher J Millard0https://orcid.org/0000-0002-1012-0829Niranjan Varma1Almutasem Saleh2https://orcid.org/0000-0002-0156-4508Kyle Morris3Peter J Watson4Andrew R Bottrill5https://orcid.org/0000-0002-5182-3643Louise Fairall6Corinne J Smith7John WR Schwabe8https://orcid.org/0000-0003-2865-4383Henry Wellcome Laboratories of Structural Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United KingdomHenry Wellcome Laboratories of Structural Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United KingdomHenry Wellcome Laboratories of Structural Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United KingdomSchool of Life Sciences, University of Warwick, Coventry, United KingdomHenry Wellcome Laboratories of Structural Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United KingdomProtein and Nucleic Acid Chemistry Laboratory, Core Biotechnology Services, University of Leicester, Leicester, United KingdomHenry Wellcome Laboratories of Structural Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United KingdomSchool of Life Sciences, University of Warwick, Coventry, United KingdomHenry Wellcome Laboratories of Structural Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United KingdomThe NuRD complex is a multi-protein transcriptional corepressor that couples histone deacetylase and ATP-dependent chromatin remodelling activities. The complex regulates the higher-order structure of chromatin, and has important roles in the regulation of gene expression, DNA damage repair and cell differentiation. HDACs 1 and 2 are recruited by the MTA1 corepressor to form the catalytic core of the complex. The histone chaperone protein RBBP4, has previously been shown to bind to the carboxy-terminal tail of MTA1. We show that MTA1 recruits a second copy of RBBP4. The crystal structure reveals an extensive interface between MTA1 and RBBP4. An EM structure, supported by SAXS and crosslinking, reveals the architecture of the dimeric HDAC1:MTA1:RBBP4 assembly which forms the core of the NuRD complex. We find evidence that in this complex RBBP4 mediates interaction with histone H3 tails, but not histone H4, suggesting a mechanism for recruitment of the NuRD complex to chromatin.https://elifesciences.org/articles/13941transcription regulationhistone deacetylaserepression complexchromatin |
| spellingShingle | Christopher J Millard Niranjan Varma Almutasem Saleh Kyle Morris Peter J Watson Andrew R Bottrill Louise Fairall Corinne J Smith John WR Schwabe The structure of the core NuRD repression complex provides insights into its interaction with chromatin eLife transcription regulation histone deacetylase repression complex chromatin |
| title | The structure of the core NuRD repression complex provides insights into its interaction with chromatin |
| title_full | The structure of the core NuRD repression complex provides insights into its interaction with chromatin |
| title_fullStr | The structure of the core NuRD repression complex provides insights into its interaction with chromatin |
| title_full_unstemmed | The structure of the core NuRD repression complex provides insights into its interaction with chromatin |
| title_short | The structure of the core NuRD repression complex provides insights into its interaction with chromatin |
| title_sort | structure of the core nurd repression complex provides insights into its interaction with chromatin |
| topic | transcription regulation histone deacetylase repression complex chromatin |
| url | https://elifesciences.org/articles/13941 |
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