Mechanism of Crosstalk between the LSD1 Demethylase and HDAC1 Deacetylase in the CoREST Complex
Summary: The transcriptional corepressor complex CoREST is one of seven histone deacetylase complexes that regulate the genome through controlling chromatin acetylation. The CoREST complex is unique in containing both histone demethylase and deacetylase enzymes, LSD1 and HDAC1, held together by the...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-02-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472030125X |
| _version_ | 1819003765248753664 |
|---|---|
| author | Yun Song Lisbeth Dagil Louise Fairall Naomi Robertson Mingxuan Wu T.J. Ragan Christos G. Savva Almutasem Saleh Nobuhiro Morone Micha B.A. Kunze Andrew G. Jamieson Philip A. Cole D. Flemming Hansen John W.R. Schwabe |
| author_facet | Yun Song Lisbeth Dagil Louise Fairall Naomi Robertson Mingxuan Wu T.J. Ragan Christos G. Savva Almutasem Saleh Nobuhiro Morone Micha B.A. Kunze Andrew G. Jamieson Philip A. Cole D. Flemming Hansen John W.R. Schwabe |
| author_sort | Yun Song |
| collection | DOAJ |
| description | Summary: The transcriptional corepressor complex CoREST is one of seven histone deacetylase complexes that regulate the genome through controlling chromatin acetylation. The CoREST complex is unique in containing both histone demethylase and deacetylase enzymes, LSD1 and HDAC1, held together by the RCOR1 scaffold protein. To date, it has been assumed that the enzymes function independently within the complex. Now, we report the assembly of the ternary complex. Using both structural and functional studies, we show that the activity of the two enzymes is closely coupled and that the complex can exist in at least two distinct states with different kinetics. Electron microscopy of the complex reveals a bi-lobed structure with LSD1 and HDAC1 enzymes at opposite ends of the complex. The structure of CoREST in complex with a nucleosome reveals a mode of chromatin engagement that contrasts with previous models. : Using a real-time NMR assay, Song et al. characterize crosstalk between LSD1 and HDAC1 in the CoREST complex. Activation or inhibition of one enzyme strongly affects activity of the other. Electron microscopy studies of the complex reveal a bi-lobed structure with implications for the mode of interaction with nucleosomes. Keywords: CoREST complex, RCOR1, HDAC1, LSD1, KDM1A, nucleosome, histone deacetylase, lysine demethylase |
| first_indexed | 2024-12-20T23:26:12Z |
| format | Article |
| id | doaj.art-b39317101c204556877f028be0770bfa |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-20T23:26:12Z |
| publishDate | 2020-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-b39317101c204556877f028be0770bfa2022-12-21T19:23:24ZengElsevierCell Reports2211-12472020-02-0130826992711.e8Mechanism of Crosstalk between the LSD1 Demethylase and HDAC1 Deacetylase in the CoREST ComplexYun Song0Lisbeth Dagil1Louise Fairall2Naomi Robertson3Mingxuan Wu4T.J. Ragan5Christos G. Savva6Almutasem Saleh7Nobuhiro Morone8Micha B.A. Kunze9Andrew G. Jamieson10Philip A. Cole11D. Flemming Hansen12John W.R. Schwabe13Leicester Institute of Chemical and Molecular Biology, Department of Molecular and Cell Biology, University of Leicester, Lancaster Road, Leicester LE1 7RH, UKInstitute of Structural and Molecular Biology, Division of Biosciences, University College London, Gower Street, London WC1E 6BT, UKLeicester Institute of Chemical and Molecular Biology, Department of Molecular and Cell Biology, University of Leicester, Lancaster Road, Leicester LE1 7RH, UKDepartment of Chemistry, University of Leicester, University Road, Leicester LE1 7RH, UKDivision of Genetics, Department of Medicine, Brigham and Women’s Hospital and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USALeicester Institute of Chemical and Molecular Biology, Department of Molecular and Cell Biology, University of Leicester, Lancaster Road, Leicester LE1 7RH, UKLeicester Institute of Chemical and Molecular Biology, Department of Molecular and Cell Biology, University of Leicester, Lancaster Road, Leicester LE1 7RH, UKLeicester Institute of Chemical and Molecular Biology, Department of Molecular and Cell Biology, University of Leicester, Lancaster Road, Leicester LE1 7RH, UKMRC-Toxicology Unit, University of Cambridge, University Road, Leicester LE1 7RH, UKInstitute of Structural and Molecular Biology, Division of Biosciences, University College London, Gower Street, London WC1E 6BT, UKDepartment of Chemistry, University of Leicester, University Road, Leicester LE1 7RH, UKDivision of Genetics, Department of Medicine, Brigham and Women’s Hospital and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USAInstitute of Structural and Molecular Biology, Division of Biosciences, University College London, Gower Street, London WC1E 6BT, UK; Corresponding authorLeicester Institute of Chemical and Molecular Biology, Department of Molecular and Cell Biology, University of Leicester, Lancaster Road, Leicester LE1 7RH, UK; Corresponding authorSummary: The transcriptional corepressor complex CoREST is one of seven histone deacetylase complexes that regulate the genome through controlling chromatin acetylation. The CoREST complex is unique in containing both histone demethylase and deacetylase enzymes, LSD1 and HDAC1, held together by the RCOR1 scaffold protein. To date, it has been assumed that the enzymes function independently within the complex. Now, we report the assembly of the ternary complex. Using both structural and functional studies, we show that the activity of the two enzymes is closely coupled and that the complex can exist in at least two distinct states with different kinetics. Electron microscopy of the complex reveals a bi-lobed structure with LSD1 and HDAC1 enzymes at opposite ends of the complex. The structure of CoREST in complex with a nucleosome reveals a mode of chromatin engagement that contrasts with previous models. : Using a real-time NMR assay, Song et al. characterize crosstalk between LSD1 and HDAC1 in the CoREST complex. Activation or inhibition of one enzyme strongly affects activity of the other. Electron microscopy studies of the complex reveal a bi-lobed structure with implications for the mode of interaction with nucleosomes. Keywords: CoREST complex, RCOR1, HDAC1, LSD1, KDM1A, nucleosome, histone deacetylase, lysine demethylasehttp://www.sciencedirect.com/science/article/pii/S221112472030125X |
| spellingShingle | Yun Song Lisbeth Dagil Louise Fairall Naomi Robertson Mingxuan Wu T.J. Ragan Christos G. Savva Almutasem Saleh Nobuhiro Morone Micha B.A. Kunze Andrew G. Jamieson Philip A. Cole D. Flemming Hansen John W.R. Schwabe Mechanism of Crosstalk between the LSD1 Demethylase and HDAC1 Deacetylase in the CoREST Complex Cell Reports |
| title | Mechanism of Crosstalk between the LSD1 Demethylase and HDAC1 Deacetylase in the CoREST Complex |
| title_full | Mechanism of Crosstalk between the LSD1 Demethylase and HDAC1 Deacetylase in the CoREST Complex |
| title_fullStr | Mechanism of Crosstalk between the LSD1 Demethylase and HDAC1 Deacetylase in the CoREST Complex |
| title_full_unstemmed | Mechanism of Crosstalk between the LSD1 Demethylase and HDAC1 Deacetylase in the CoREST Complex |
| title_short | Mechanism of Crosstalk between the LSD1 Demethylase and HDAC1 Deacetylase in the CoREST Complex |
| title_sort | mechanism of crosstalk between the lsd1 demethylase and hdac1 deacetylase in the corest complex |
| url | http://www.sciencedirect.com/science/article/pii/S221112472030125X |
| work_keys_str_mv | AT yunsong mechanismofcrosstalkbetweenthelsd1demethylaseandhdac1deacetylaseinthecorestcomplex AT lisbethdagil mechanismofcrosstalkbetweenthelsd1demethylaseandhdac1deacetylaseinthecorestcomplex AT louisefairall mechanismofcrosstalkbetweenthelsd1demethylaseandhdac1deacetylaseinthecorestcomplex AT naomirobertson mechanismofcrosstalkbetweenthelsd1demethylaseandhdac1deacetylaseinthecorestcomplex AT mingxuanwu mechanismofcrosstalkbetweenthelsd1demethylaseandhdac1deacetylaseinthecorestcomplex AT tjragan mechanismofcrosstalkbetweenthelsd1demethylaseandhdac1deacetylaseinthecorestcomplex AT christosgsavva mechanismofcrosstalkbetweenthelsd1demethylaseandhdac1deacetylaseinthecorestcomplex AT almutasemsaleh mechanismofcrosstalkbetweenthelsd1demethylaseandhdac1deacetylaseinthecorestcomplex AT nobuhiromorone mechanismofcrosstalkbetweenthelsd1demethylaseandhdac1deacetylaseinthecorestcomplex AT michabakunze mechanismofcrosstalkbetweenthelsd1demethylaseandhdac1deacetylaseinthecorestcomplex AT andrewgjamieson mechanismofcrosstalkbetweenthelsd1demethylaseandhdac1deacetylaseinthecorestcomplex AT philipacole mechanismofcrosstalkbetweenthelsd1demethylaseandhdac1deacetylaseinthecorestcomplex AT dflemminghansen mechanismofcrosstalkbetweenthelsd1demethylaseandhdac1deacetylaseinthecorestcomplex AT johnwrschwabe mechanismofcrosstalkbetweenthelsd1demethylaseandhdac1deacetylaseinthecorestcomplex |