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Insights into a novel nuclear function for Fascin in the regulation of the amino-acid transporter SLC3A2
Fascin 1 (FSCN1) is a cytoskeleton-associated protein recognized to function primarily in the regulation of cytoskeleton structure and formation of plasma membrane protrusions. Here we report a novel nuclear function for Fascin 1. Biochemical studies and genome wide localization using ChIP-seq ident...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098188/ https://www.ncbi.nlm.nih.gov/pubmed/27819326 http://dx.doi.org/10.1038/srep36699 |
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author | Saad, Amine Bijian, Krikor Qiu, Dinghong da Silva, Sabrina Daniela Marques, Maud Chang, Chia-Hao Nassour, Hassan Ramotar, Dindial Damaraju, Sambasivarao Mackey, John Bismar, Tarek Witcher, Michael Alaoui-Jamali, Moulay A. |
author_facet | Saad, Amine Bijian, Krikor Qiu, Dinghong da Silva, Sabrina Daniela Marques, Maud Chang, Chia-Hao Nassour, Hassan Ramotar, Dindial Damaraju, Sambasivarao Mackey, John Bismar, Tarek Witcher, Michael Alaoui-Jamali, Moulay A. |
author_sort | Saad, Amine |
collection | PubMed |
description | Fascin 1 (FSCN1) is a cytoskeleton-associated protein recognized to function primarily in the regulation of cytoskeleton structure and formation of plasma membrane protrusions. Here we report a novel nuclear function for Fascin 1. Biochemical studies and genome wide localization using ChIP-seq identified phosphorylated Fascin 1 (pFascin) in complexes associated with transcription and that it co-localizes with histone H3 Lys4 trimethylation (H3K4me3) on chromatin. Gene expression profiling identified genes affected by Fascin 1 including SLC3A2, a gene encoding for a plasma membrane transporter that regulates intracellular amino acid levels. RbBP5, a subunit of the H3K4 histone methyltransferase (HMT) complex was found to interact with Fascin 1 supporting its role in H3K4me3 establishment at target genes. Moreover, we show that changes to SLC3A2 levels affect amino acid-mediated mTORC1 activation. These results reveal that Fascin 1 has a yet undiscovered nuclear function as an epigenetic modulator of genes essential for amino acid metabolism. |
format | Online Article Text |
id | pubmed-5098188 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-50981882016-11-10 Insights into a novel nuclear function for Fascin in the regulation of the amino-acid transporter SLC3A2 Saad, Amine Bijian, Krikor Qiu, Dinghong da Silva, Sabrina Daniela Marques, Maud Chang, Chia-Hao Nassour, Hassan Ramotar, Dindial Damaraju, Sambasivarao Mackey, John Bismar, Tarek Witcher, Michael Alaoui-Jamali, Moulay A. Sci Rep Article Fascin 1 (FSCN1) is a cytoskeleton-associated protein recognized to function primarily in the regulation of cytoskeleton structure and formation of plasma membrane protrusions. Here we report a novel nuclear function for Fascin 1. Biochemical studies and genome wide localization using ChIP-seq identified phosphorylated Fascin 1 (pFascin) in complexes associated with transcription and that it co-localizes with histone H3 Lys4 trimethylation (H3K4me3) on chromatin. Gene expression profiling identified genes affected by Fascin 1 including SLC3A2, a gene encoding for a plasma membrane transporter that regulates intracellular amino acid levels. RbBP5, a subunit of the H3K4 histone methyltransferase (HMT) complex was found to interact with Fascin 1 supporting its role in H3K4me3 establishment at target genes. Moreover, we show that changes to SLC3A2 levels affect amino acid-mediated mTORC1 activation. These results reveal that Fascin 1 has a yet undiscovered nuclear function as an epigenetic modulator of genes essential for amino acid metabolism. Nature Publishing Group 2016-11-07 /pmc/articles/PMC5098188/ /pubmed/27819326 http://dx.doi.org/10.1038/srep36699 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Saad, Amine Bijian, Krikor Qiu, Dinghong da Silva, Sabrina Daniela Marques, Maud Chang, Chia-Hao Nassour, Hassan Ramotar, Dindial Damaraju, Sambasivarao Mackey, John Bismar, Tarek Witcher, Michael Alaoui-Jamali, Moulay A. Insights into a novel nuclear function for Fascin in the regulation of the amino-acid transporter SLC3A2 |
title | Insights into a novel nuclear function for Fascin in the regulation of the amino-acid transporter SLC3A2 |
title_full | Insights into a novel nuclear function for Fascin in the regulation of the amino-acid transporter SLC3A2 |
title_fullStr | Insights into a novel nuclear function for Fascin in the regulation of the amino-acid transporter SLC3A2 |
title_full_unstemmed | Insights into a novel nuclear function for Fascin in the regulation of the amino-acid transporter SLC3A2 |
title_short | Insights into a novel nuclear function for Fascin in the regulation of the amino-acid transporter SLC3A2 |
title_sort | insights into a novel nuclear function for fascin in the regulation of the amino-acid transporter slc3a2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098188/ https://www.ncbi.nlm.nih.gov/pubmed/27819326 http://dx.doi.org/10.1038/srep36699 |
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