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Mechanism of Crosstalk between the LSD1 Demethylase and HDAC1 Deacetylase in the CoREST Complex

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journal contribution
posted on 12.03.2021, 16:50 by Yun Song, Lisbeth Dagil, Louise Fairall, Naomi Robertson, Mingxuan Wu, TJ Ragan, Christos G Savva, Almutasem Saleh, Nobuhiro Morone, Micha BA Kunze, Andrew G Jamieson, Philip A Cole, D Flemming Hansen, John WR Schwabe
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.

History

Citation

Cell Reports, Volume 30, Issue 8, 25 February 2020, Pages 2699-2711.e8

Author affiliation

Department of Chemistry

Version

VoR (Version of Record)

Published in

Cell Reports

Volume

30

Issue

8

Pagination

2699-2711.e8

Publisher

Elsevier

issn

2211-1247

eissn

2211-1247

Acceptance date

24/01/2020

Copyright date

2020

Spatial coverage

United States

Language

English