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An interaction network of mental disorder proteins in neural stem cells
Mental disorders (MDs) such as intellectual disability (ID), autism spectrum disorders (ASD) and schizophrenia have a strong genetic component. Recently, many gene mutations associated with ID, ASD or schizophrenia have been identified by high-throughput sequencing. A substantial fraction of these m...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5416693/ https://www.ncbi.nlm.nih.gov/pubmed/28375211 http://dx.doi.org/10.1038/tp.2017.52 |
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author | Moen, M J Adams, H H H Brandsma, J H Dekkers, D H W Akinci, U Karkampouna, S Quevedo, M Kockx, C E M Ozgür, Z van IJcken, W F J Demmers, J Poot, R A |
author_facet | Moen, M J Adams, H H H Brandsma, J H Dekkers, D H W Akinci, U Karkampouna, S Quevedo, M Kockx, C E M Ozgür, Z van IJcken, W F J Demmers, J Poot, R A |
author_sort | Moen, M J |
collection | PubMed |
description | Mental disorders (MDs) such as intellectual disability (ID), autism spectrum disorders (ASD) and schizophrenia have a strong genetic component. Recently, many gene mutations associated with ID, ASD or schizophrenia have been identified by high-throughput sequencing. A substantial fraction of these mutations are in genes encoding transcriptional regulators. Transcriptional regulators associated with different MDs but acting in the same gene regulatory network provide information on the molecular relation between MDs. Physical interaction between transcriptional regulators is a strong predictor for their cooperation in gene regulation. Here, we biochemically purified transcriptional regulators from neural stem cells, identified their interaction partners by mass spectrometry and assembled a protein interaction network containing 206 proteins, including 68 proteins mutated in MD patients and 52 proteins significantly lacking coding variation in humans. Our network shows molecular connections between established MD proteins and provides a discovery tool for novel MD genes. Network proteins preferentially co-localize on the genome and cooperate in disease-relevant gene regulation. Our results suggest that the observed transcriptional regulators associated with ID, ASD or schizophrenia are part of a transcriptional network in neural stem cells. We find that more severe mutations in network proteins are associated with MDs that include lower intelligence quotient (IQ), suggesting that the level of disruption of a shared transcriptional network correlates with cognitive dysfunction. |
format | Online Article Text |
id | pubmed-5416693 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-54166932017-05-16 An interaction network of mental disorder proteins in neural stem cells Moen, M J Adams, H H H Brandsma, J H Dekkers, D H W Akinci, U Karkampouna, S Quevedo, M Kockx, C E M Ozgür, Z van IJcken, W F J Demmers, J Poot, R A Transl Psychiatry Original Article Mental disorders (MDs) such as intellectual disability (ID), autism spectrum disorders (ASD) and schizophrenia have a strong genetic component. Recently, many gene mutations associated with ID, ASD or schizophrenia have been identified by high-throughput sequencing. A substantial fraction of these mutations are in genes encoding transcriptional regulators. Transcriptional regulators associated with different MDs but acting in the same gene regulatory network provide information on the molecular relation between MDs. Physical interaction between transcriptional regulators is a strong predictor for their cooperation in gene regulation. Here, we biochemically purified transcriptional regulators from neural stem cells, identified their interaction partners by mass spectrometry and assembled a protein interaction network containing 206 proteins, including 68 proteins mutated in MD patients and 52 proteins significantly lacking coding variation in humans. Our network shows molecular connections between established MD proteins and provides a discovery tool for novel MD genes. Network proteins preferentially co-localize on the genome and cooperate in disease-relevant gene regulation. Our results suggest that the observed transcriptional regulators associated with ID, ASD or schizophrenia are part of a transcriptional network in neural stem cells. We find that more severe mutations in network proteins are associated with MDs that include lower intelligence quotient (IQ), suggesting that the level of disruption of a shared transcriptional network correlates with cognitive dysfunction. Nature Publishing Group 2017-04 2017-04-04 /pmc/articles/PMC5416693/ /pubmed/28375211 http://dx.doi.org/10.1038/tp.2017.52 Text en Copyright © 2017 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 | Original Article Moen, M J Adams, H H H Brandsma, J H Dekkers, D H W Akinci, U Karkampouna, S Quevedo, M Kockx, C E M Ozgür, Z van IJcken, W F J Demmers, J Poot, R A An interaction network of mental disorder proteins in neural stem cells |
title | An interaction network of mental disorder proteins in neural stem cells |
title_full | An interaction network of mental disorder proteins in neural stem cells |
title_fullStr | An interaction network of mental disorder proteins in neural stem cells |
title_full_unstemmed | An interaction network of mental disorder proteins in neural stem cells |
title_short | An interaction network of mental disorder proteins in neural stem cells |
title_sort | interaction network of mental disorder proteins in neural stem cells |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5416693/ https://www.ncbi.nlm.nih.gov/pubmed/28375211 http://dx.doi.org/10.1038/tp.2017.52 |
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