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Histone posttranslational modifications predict specific alternative exon subtypes in mammalian brain

A compelling body of literature, based on next generation chromatin immunoprecipitation and RNA sequencing of reward brain regions indicates that the regulation of the epigenetic landscape likely underlies chronic drug abuse and addiction. It is now critical to develop highly innovative computationa...

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Autores principales: Hu, Qiwen, Kim, Eun Ji, Feng, Jian, Grant, Gregory R., Heller, Elizabeth A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487056/
https://www.ncbi.nlm.nih.gov/pubmed/28609483
http://dx.doi.org/10.1371/journal.pcbi.1005602
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author Hu, Qiwen
Kim, Eun Ji
Feng, Jian
Grant, Gregory R.
Heller, Elizabeth A.
author_facet Hu, Qiwen
Kim, Eun Ji
Feng, Jian
Grant, Gregory R.
Heller, Elizabeth A.
author_sort Hu, Qiwen
collection PubMed
description A compelling body of literature, based on next generation chromatin immunoprecipitation and RNA sequencing of reward brain regions indicates that the regulation of the epigenetic landscape likely underlies chronic drug abuse and addiction. It is now critical to develop highly innovative computational strategies to reveal the relevant regulatory transcriptional mechanisms that may underlie neuropsychiatric disease. We have analyzed chromatin regulation of alternative splicing, which is implicated in cocaine exposure in mice. Recent literature has described chromatin-regulated alternative splicing, suggesting a novel function for drug-induced neuroepigenetic remodeling. However, the extent of the genome-wide association between particular histone modifications and alternative splicing remains unexplored. To address this, we have developed novel computational approaches to model the association between alternative splicing and histone posttranslational modifications in the nucleus accumbens (NAc), a brain reward region. Using classical statistical methods and machine learning to combine ChIP-Seq and RNA-Seq data, we found that specific histone modifications are strongly associated with various aspects of differential splicing. H3K36me3 and H3K4me1 have the strongest association with splicing indicating they play a significant role in alternative splicing in brain reward tissue.
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spelling pubmed-54870562017-07-11 Histone posttranslational modifications predict specific alternative exon subtypes in mammalian brain Hu, Qiwen Kim, Eun Ji Feng, Jian Grant, Gregory R. Heller, Elizabeth A. PLoS Comput Biol Research Article A compelling body of literature, based on next generation chromatin immunoprecipitation and RNA sequencing of reward brain regions indicates that the regulation of the epigenetic landscape likely underlies chronic drug abuse and addiction. It is now critical to develop highly innovative computational strategies to reveal the relevant regulatory transcriptional mechanisms that may underlie neuropsychiatric disease. We have analyzed chromatin regulation of alternative splicing, which is implicated in cocaine exposure in mice. Recent literature has described chromatin-regulated alternative splicing, suggesting a novel function for drug-induced neuroepigenetic remodeling. However, the extent of the genome-wide association between particular histone modifications and alternative splicing remains unexplored. To address this, we have developed novel computational approaches to model the association between alternative splicing and histone posttranslational modifications in the nucleus accumbens (NAc), a brain reward region. Using classical statistical methods and machine learning to combine ChIP-Seq and RNA-Seq data, we found that specific histone modifications are strongly associated with various aspects of differential splicing. H3K36me3 and H3K4me1 have the strongest association with splicing indicating they play a significant role in alternative splicing in brain reward tissue. Public Library of Science 2017-06-13 /pmc/articles/PMC5487056/ /pubmed/28609483 http://dx.doi.org/10.1371/journal.pcbi.1005602 Text en © 2017 Hu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hu, Qiwen
Kim, Eun Ji
Feng, Jian
Grant, Gregory R.
Heller, Elizabeth A.
Histone posttranslational modifications predict specific alternative exon subtypes in mammalian brain
title Histone posttranslational modifications predict specific alternative exon subtypes in mammalian brain
title_full Histone posttranslational modifications predict specific alternative exon subtypes in mammalian brain
title_fullStr Histone posttranslational modifications predict specific alternative exon subtypes in mammalian brain
title_full_unstemmed Histone posttranslational modifications predict specific alternative exon subtypes in mammalian brain
title_short Histone posttranslational modifications predict specific alternative exon subtypes in mammalian brain
title_sort histone posttranslational modifications predict specific alternative exon subtypes in mammalian brain
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487056/
https://www.ncbi.nlm.nih.gov/pubmed/28609483
http://dx.doi.org/10.1371/journal.pcbi.1005602
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