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ZNF198 Stabilizes the LSD1–CoREST–HDAC1 Complex on Chromatin through Its MYM-Type Zinc Fingers
Histone modifications in chromatin regulate gene expression. A transcriptional co-repressor complex containing LSD1–CoREST–HDAC1 (termed LCH hereafter for simplicity) represses transcription by coordinately removing histone modifications associated with transcriptional activation. RE1-silencing tran...
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532748/ https://www.ncbi.nlm.nih.gov/pubmed/18806873 http://dx.doi.org/10.1371/journal.pone.0003255 |
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author | Gocke, Christian B. Yu, Hongtao |
author_facet | Gocke, Christian B. Yu, Hongtao |
author_sort | Gocke, Christian B. |
collection | PubMed |
description | Histone modifications in chromatin regulate gene expression. A transcriptional co-repressor complex containing LSD1–CoREST–HDAC1 (termed LCH hereafter for simplicity) represses transcription by coordinately removing histone modifications associated with transcriptional activation. RE1-silencing transcription factor (REST) recruits LCH to the promoters of neuron-specific genes, thereby silencing their transcription in non-neuronal tissues. ZNF198 is a member of a family of MYM-type zinc finger proteins that associate with LCH. Here, we show that ZNF198-like proteins are required for the repression of E-cadherin (a gene known to be repressed by LSD1), but not REST-responsive genes. ZNF198 binds preferentially to the intact LCH ternary complex, but not its individual subunits. ZNF198- and REST-binding to the LCH complex are mutually exclusive. ZNF198 associates with chromatin independently of LCH. Furthermore, modification of HDAC1 by small ubiquitin-like modifier (SUMO) in vitro weakens its interaction with CoREST whereas sumoylation of HDAC1 stimulates its binding to ZNF198. Finally, we mapped the LCH- and HDAC1–SUMO-binding domains of ZNF198 to tandem repeats of MYM-type zinc fingers. Therefore, our results suggest that ZNF198, through its multiple protein-protein interaction interfaces, helps to maintain the intact LCH complex on specific, non-REST-responsive promoters and may also prevent SUMO-dependent dissociation of HDAC1. |
format | Text |
id | pubmed-2532748 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-25327482008-09-22 ZNF198 Stabilizes the LSD1–CoREST–HDAC1 Complex on Chromatin through Its MYM-Type Zinc Fingers Gocke, Christian B. Yu, Hongtao PLoS One Research Article Histone modifications in chromatin regulate gene expression. A transcriptional co-repressor complex containing LSD1–CoREST–HDAC1 (termed LCH hereafter for simplicity) represses transcription by coordinately removing histone modifications associated with transcriptional activation. RE1-silencing transcription factor (REST) recruits LCH to the promoters of neuron-specific genes, thereby silencing their transcription in non-neuronal tissues. ZNF198 is a member of a family of MYM-type zinc finger proteins that associate with LCH. Here, we show that ZNF198-like proteins are required for the repression of E-cadherin (a gene known to be repressed by LSD1), but not REST-responsive genes. ZNF198 binds preferentially to the intact LCH ternary complex, but not its individual subunits. ZNF198- and REST-binding to the LCH complex are mutually exclusive. ZNF198 associates with chromatin independently of LCH. Furthermore, modification of HDAC1 by small ubiquitin-like modifier (SUMO) in vitro weakens its interaction with CoREST whereas sumoylation of HDAC1 stimulates its binding to ZNF198. Finally, we mapped the LCH- and HDAC1–SUMO-binding domains of ZNF198 to tandem repeats of MYM-type zinc fingers. Therefore, our results suggest that ZNF198, through its multiple protein-protein interaction interfaces, helps to maintain the intact LCH complex on specific, non-REST-responsive promoters and may also prevent SUMO-dependent dissociation of HDAC1. Public Library of Science 2008-09-22 /pmc/articles/PMC2532748/ /pubmed/18806873 http://dx.doi.org/10.1371/journal.pone.0003255 Text en Gocke, Yu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Gocke, Christian B. Yu, Hongtao ZNF198 Stabilizes the LSD1–CoREST–HDAC1 Complex on Chromatin through Its MYM-Type Zinc Fingers |
title | ZNF198 Stabilizes the LSD1–CoREST–HDAC1 Complex on Chromatin through Its MYM-Type Zinc Fingers |
title_full | ZNF198 Stabilizes the LSD1–CoREST–HDAC1 Complex on Chromatin through Its MYM-Type Zinc Fingers |
title_fullStr | ZNF198 Stabilizes the LSD1–CoREST–HDAC1 Complex on Chromatin through Its MYM-Type Zinc Fingers |
title_full_unstemmed | ZNF198 Stabilizes the LSD1–CoREST–HDAC1 Complex on Chromatin through Its MYM-Type Zinc Fingers |
title_short | ZNF198 Stabilizes the LSD1–CoREST–HDAC1 Complex on Chromatin through Its MYM-Type Zinc Fingers |
title_sort | znf198 stabilizes the lsd1–corest–hdac1 complex on chromatin through its mym-type zinc fingers |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532748/ https://www.ncbi.nlm.nih.gov/pubmed/18806873 http://dx.doi.org/10.1371/journal.pone.0003255 |
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