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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
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.
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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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