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Differential HDAC1/2 network analysis reveals a role for prefoldin/CCT in HDAC1/2 complex assembly
HDAC1 and HDAC2 are components of several corepressor complexes (NuRD, Sin3, CoREST and MiDAC) that regulate transcription by deacetylating histones resulting in a more compact chromatin environment. This limits access of transcriptional machinery to genes and silences transcription. While using an...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135828/ https://www.ncbi.nlm.nih.gov/pubmed/30209338 http://dx.doi.org/10.1038/s41598-018-32009-w |
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author | Banks, Charles A. S. Miah, Sayem Adams, Mark K. Eubanks, Cassandra G. Thornton, Janet L. Florens, Laurence Washburn, Michael P. |
author_facet | Banks, Charles A. S. Miah, Sayem Adams, Mark K. Eubanks, Cassandra G. Thornton, Janet L. Florens, Laurence Washburn, Michael P. |
author_sort | Banks, Charles A. S. |
collection | PubMed |
description | HDAC1 and HDAC2 are components of several corepressor complexes (NuRD, Sin3, CoREST and MiDAC) that regulate transcription by deacetylating histones resulting in a more compact chromatin environment. This limits access of transcriptional machinery to genes and silences transcription. While using an AP-MS approach to map HDAC1/2 protein interaction networks, we noticed that N-terminally tagged versions of HDAC1 and HDAC2 did not assemble into HDAC corepressor complexes as expected, but instead appeared to be stalled with components of the prefoldin-CCT chaperonin pathway. These N-terminally tagged HDACs were also catalytically inactive. In contrast to the N-terminally tagged HDACs, C-terminally tagged HDAC1 and HDAC2 captured complete histone deacetylase complexes and the purified proteins had deacetylation activity that could be inhibited by SAHA (Vorinostat), a Class I/II HDAC inhibitor. This tag-mediated reprogramming of the HDAC1/2 protein interaction network suggests a mechanism whereby HDAC1 is first loaded into the CCT complex by prefoldin to complete folding, and then assembled into active, functional HDAC complexes. Imaging revealed that the prefoldin subunit VBP1 colocalises with nuclear HDAC1, suggesting that delivery of HDAC1 to the CCT complex happens in the nucleus. |
format | Online Article Text |
id | pubmed-6135828 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61358282018-09-15 Differential HDAC1/2 network analysis reveals a role for prefoldin/CCT in HDAC1/2 complex assembly Banks, Charles A. S. Miah, Sayem Adams, Mark K. Eubanks, Cassandra G. Thornton, Janet L. Florens, Laurence Washburn, Michael P. Sci Rep Article HDAC1 and HDAC2 are components of several corepressor complexes (NuRD, Sin3, CoREST and MiDAC) that regulate transcription by deacetylating histones resulting in a more compact chromatin environment. This limits access of transcriptional machinery to genes and silences transcription. While using an AP-MS approach to map HDAC1/2 protein interaction networks, we noticed that N-terminally tagged versions of HDAC1 and HDAC2 did not assemble into HDAC corepressor complexes as expected, but instead appeared to be stalled with components of the prefoldin-CCT chaperonin pathway. These N-terminally tagged HDACs were also catalytically inactive. In contrast to the N-terminally tagged HDACs, C-terminally tagged HDAC1 and HDAC2 captured complete histone deacetylase complexes and the purified proteins had deacetylation activity that could be inhibited by SAHA (Vorinostat), a Class I/II HDAC inhibitor. This tag-mediated reprogramming of the HDAC1/2 protein interaction network suggests a mechanism whereby HDAC1 is first loaded into the CCT complex by prefoldin to complete folding, and then assembled into active, functional HDAC complexes. Imaging revealed that the prefoldin subunit VBP1 colocalises with nuclear HDAC1, suggesting that delivery of HDAC1 to the CCT complex happens in the nucleus. Nature Publishing Group UK 2018-09-12 /pmc/articles/PMC6135828/ /pubmed/30209338 http://dx.doi.org/10.1038/s41598-018-32009-w Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Banks, Charles A. S. Miah, Sayem Adams, Mark K. Eubanks, Cassandra G. Thornton, Janet L. Florens, Laurence Washburn, Michael P. Differential HDAC1/2 network analysis reveals a role for prefoldin/CCT in HDAC1/2 complex assembly |
title | Differential HDAC1/2 network analysis reveals a role for prefoldin/CCT in HDAC1/2 complex assembly |
title_full | Differential HDAC1/2 network analysis reveals a role for prefoldin/CCT in HDAC1/2 complex assembly |
title_fullStr | Differential HDAC1/2 network analysis reveals a role for prefoldin/CCT in HDAC1/2 complex assembly |
title_full_unstemmed | Differential HDAC1/2 network analysis reveals a role for prefoldin/CCT in HDAC1/2 complex assembly |
title_short | Differential HDAC1/2 network analysis reveals a role for prefoldin/CCT in HDAC1/2 complex assembly |
title_sort | differential hdac1/2 network analysis reveals a role for prefoldin/cct in hdac1/2 complex assembly |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135828/ https://www.ncbi.nlm.nih.gov/pubmed/30209338 http://dx.doi.org/10.1038/s41598-018-32009-w |
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