Maintenance of silent chromatin through replication requires SWI/SNF-like chromatin remodeler SMARCAD1.

Epigenetic marks such as posttranslational histone modifications specify the functional states of underlying DNA sequences, though how they are maintained after their disruption during DNA replication remains a critical question. We identify the mammalian SWI/SNF-like protein SMARCAD1 as a key facto...

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Main Authors: Rowbotham, S, Barki, L, Neves-Costa, A, Santos, F, Dean, W, Hawkes, N, Choudhary, P, Will, W, Webster, J, Oxley, D, Green, C, Varga-Weisz, P, Mermoud, J
Format: Journal article
Language:English
Published: 2011
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author Rowbotham, S
Barki, L
Neves-Costa, A
Santos, F
Dean, W
Hawkes, N
Choudhary, P
Will, W
Webster, J
Oxley, D
Green, C
Varga-Weisz, P
Mermoud, J
author_facet Rowbotham, S
Barki, L
Neves-Costa, A
Santos, F
Dean, W
Hawkes, N
Choudhary, P
Will, W
Webster, J
Oxley, D
Green, C
Varga-Weisz, P
Mermoud, J
author_sort Rowbotham, S
collection OXFORD
description Epigenetic marks such as posttranslational histone modifications specify the functional states of underlying DNA sequences, though how they are maintained after their disruption during DNA replication remains a critical question. We identify the mammalian SWI/SNF-like protein SMARCAD1 as a key factor required for the re-establishment of repressive chromatin. The ATPase activity of SMARCAD1 is necessary for global deacetylation of histones H3/H4. In this way, SMARCAD1 promotes methylation of H3K9, the establishment of heterochromatin, and faithful chromosome segregation. SMARCAD1 associates with transcriptional repressors including KAP1, histone deacetylases HDAC1/2 and the histone methyltransferase G9a/GLP and modulates the interaction of HDAC1 and KAP1 with heterochromatin. SMARCAD1 directly interacts with PCNA, a central component of the replication machinery, and is recruited to sites of DNA replication. Our findings suggest that chromatin remodeling by SMARCAD1 ensures that silenced loci, such as pericentric heterochromatin, are correctly perpetuated.
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spelling oxford-uuid:7142a5c1-5283-4c9e-b480-8507466c69dd2022-03-26T19:42:29ZMaintenance of silent chromatin through replication requires SWI/SNF-like chromatin remodeler SMARCAD1.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7142a5c1-5283-4c9e-b480-8507466c69ddEnglishSymplectic Elements at Oxford2011Rowbotham, SBarki, LNeves-Costa, ASantos, FDean, WHawkes, NChoudhary, PWill, WWebster, JOxley, DGreen, CVarga-Weisz, PMermoud, JEpigenetic marks such as posttranslational histone modifications specify the functional states of underlying DNA sequences, though how they are maintained after their disruption during DNA replication remains a critical question. We identify the mammalian SWI/SNF-like protein SMARCAD1 as a key factor required for the re-establishment of repressive chromatin. The ATPase activity of SMARCAD1 is necessary for global deacetylation of histones H3/H4. In this way, SMARCAD1 promotes methylation of H3K9, the establishment of heterochromatin, and faithful chromosome segregation. SMARCAD1 associates with transcriptional repressors including KAP1, histone deacetylases HDAC1/2 and the histone methyltransferase G9a/GLP and modulates the interaction of HDAC1 and KAP1 with heterochromatin. SMARCAD1 directly interacts with PCNA, a central component of the replication machinery, and is recruited to sites of DNA replication. Our findings suggest that chromatin remodeling by SMARCAD1 ensures that silenced loci, such as pericentric heterochromatin, are correctly perpetuated.
spellingShingle Rowbotham, S
Barki, L
Neves-Costa, A
Santos, F
Dean, W
Hawkes, N
Choudhary, P
Will, W
Webster, J
Oxley, D
Green, C
Varga-Weisz, P
Mermoud, J
Maintenance of silent chromatin through replication requires SWI/SNF-like chromatin remodeler SMARCAD1.
title Maintenance of silent chromatin through replication requires SWI/SNF-like chromatin remodeler SMARCAD1.
title_full Maintenance of silent chromatin through replication requires SWI/SNF-like chromatin remodeler SMARCAD1.
title_fullStr Maintenance of silent chromatin through replication requires SWI/SNF-like chromatin remodeler SMARCAD1.
title_full_unstemmed Maintenance of silent chromatin through replication requires SWI/SNF-like chromatin remodeler SMARCAD1.
title_short Maintenance of silent chromatin through replication requires SWI/SNF-like chromatin remodeler SMARCAD1.
title_sort maintenance of silent chromatin through replication requires swi snf like chromatin remodeler smarcad1
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