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Post-translational modification localizes MYC to the nuclear pore basket to regulate a subset of target genes involved in cellular responses to environmental signals

The transcription factor MYC (also c-Myc) induces histone modification, chromatin remodeling, and the release of paused RNA polymerase to broadly regulate transcription. MYC is subject to a series of post-translational modifications that affect its stability and oncogenic activity, but how these con...

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Autores principales: Su, Yulong, Pelz, Carl, Huang, Tao, Torkenczy, Kristof, Wang, Xiaoyan, Cherry, Allison, Daniel, Colin J., Liang, Juan, Nan, Xiaolin, Dai, Mu-Shui, Adey, Andrew, Impey, Soren, Sears, Rosalie C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217735/
https://www.ncbi.nlm.nih.gov/pubmed/30366908
http://dx.doi.org/10.1101/gad.314377.118
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author Su, Yulong
Pelz, Carl
Huang, Tao
Torkenczy, Kristof
Wang, Xiaoyan
Cherry, Allison
Daniel, Colin J.
Liang, Juan
Nan, Xiaolin
Dai, Mu-Shui
Adey, Andrew
Impey, Soren
Sears, Rosalie C.
author_facet Su, Yulong
Pelz, Carl
Huang, Tao
Torkenczy, Kristof
Wang, Xiaoyan
Cherry, Allison
Daniel, Colin J.
Liang, Juan
Nan, Xiaolin
Dai, Mu-Shui
Adey, Andrew
Impey, Soren
Sears, Rosalie C.
author_sort Su, Yulong
collection PubMed
description The transcription factor MYC (also c-Myc) induces histone modification, chromatin remodeling, and the release of paused RNA polymerase to broadly regulate transcription. MYC is subject to a series of post-translational modifications that affect its stability and oncogenic activity, but how these control MYC's function on the genome is largely unknown. Recent work demonstrates an intimate connection between nuclear compartmentalization and gene regulation. Here, we report that Ser62 phosphorylation and PIN1-mediated isomerization of MYC dynamically regulate the spatial distribution of MYC in the nucleus, promoting its association with the inner basket of the nuclear pore in response to proliferative signals, where it recruits the histone acetyltransferase GCN5 to bind and regulate local gene acetylation and expression. We demonstrate that PIN1-mediated localization of MYC to the nuclear pore regulates MYC target genes responsive to mitogen stimulation that are involved in proliferation and migration pathways. These changes are also present at the chromatin level, with an increase in open regulatory elements in response to stimulation that is PIN1-dependent and associated with MYC chromatin binding. Taken together, our study indicates that post-translational modification of MYC controls its spatial activity to optimally regulate gene expression in response to extrinsic signals in normal and diseased states.
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spelling pubmed-62177352018-11-14 Post-translational modification localizes MYC to the nuclear pore basket to regulate a subset of target genes involved in cellular responses to environmental signals Su, Yulong Pelz, Carl Huang, Tao Torkenczy, Kristof Wang, Xiaoyan Cherry, Allison Daniel, Colin J. Liang, Juan Nan, Xiaolin Dai, Mu-Shui Adey, Andrew Impey, Soren Sears, Rosalie C. Genes Dev Research Paper The transcription factor MYC (also c-Myc) induces histone modification, chromatin remodeling, and the release of paused RNA polymerase to broadly regulate transcription. MYC is subject to a series of post-translational modifications that affect its stability and oncogenic activity, but how these control MYC's function on the genome is largely unknown. Recent work demonstrates an intimate connection between nuclear compartmentalization and gene regulation. Here, we report that Ser62 phosphorylation and PIN1-mediated isomerization of MYC dynamically regulate the spatial distribution of MYC in the nucleus, promoting its association with the inner basket of the nuclear pore in response to proliferative signals, where it recruits the histone acetyltransferase GCN5 to bind and regulate local gene acetylation and expression. We demonstrate that PIN1-mediated localization of MYC to the nuclear pore regulates MYC target genes responsive to mitogen stimulation that are involved in proliferation and migration pathways. These changes are also present at the chromatin level, with an increase in open regulatory elements in response to stimulation that is PIN1-dependent and associated with MYC chromatin binding. Taken together, our study indicates that post-translational modification of MYC controls its spatial activity to optimally regulate gene expression in response to extrinsic signals in normal and diseased states. Cold Spring Harbor Laboratory Press 2018-11-01 /pmc/articles/PMC6217735/ /pubmed/30366908 http://dx.doi.org/10.1101/gad.314377.118 Text en © 2018 Su et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Su, Yulong
Pelz, Carl
Huang, Tao
Torkenczy, Kristof
Wang, Xiaoyan
Cherry, Allison
Daniel, Colin J.
Liang, Juan
Nan, Xiaolin
Dai, Mu-Shui
Adey, Andrew
Impey, Soren
Sears, Rosalie C.
Post-translational modification localizes MYC to the nuclear pore basket to regulate a subset of target genes involved in cellular responses to environmental signals
title Post-translational modification localizes MYC to the nuclear pore basket to regulate a subset of target genes involved in cellular responses to environmental signals
title_full Post-translational modification localizes MYC to the nuclear pore basket to regulate a subset of target genes involved in cellular responses to environmental signals
title_fullStr Post-translational modification localizes MYC to the nuclear pore basket to regulate a subset of target genes involved in cellular responses to environmental signals
title_full_unstemmed Post-translational modification localizes MYC to the nuclear pore basket to regulate a subset of target genes involved in cellular responses to environmental signals
title_short Post-translational modification localizes MYC to the nuclear pore basket to regulate a subset of target genes involved in cellular responses to environmental signals
title_sort post-translational modification localizes myc to the nuclear pore basket to regulate a subset of target genes involved in cellular responses to environmental signals
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217735/
https://www.ncbi.nlm.nih.gov/pubmed/30366908
http://dx.doi.org/10.1101/gad.314377.118
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