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ACF chromatin remodeling complex mediates stress–induced depressive–like behavior
Improved treatment for major depressive disorder (MDD) remains elusive due to limited understanding of its underlying biological mechanisms. Stress–induced maladaptive transcriptional regulation within limbic neural circuits likely contributes to the development of MDD, possibly through epigenetic f...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598281/ https://www.ncbi.nlm.nih.gov/pubmed/26390241 http://dx.doi.org/10.1038/nm.3939 |
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author | Sun, HaoSheng Damez–Werno, Diane M. Scobie, Kimberly N. Shao, Ning–Yi Dias, Caroline Rabkin, Jacqui Koo, Ja Wook Korb, Erica Bagot, Rosemary C. Ahn, Francisca H. Cahill, Michael E. Labonté, Benoit Mouzon, Ezekiell Heller, Elizabeth A. Cates, Hannah Golden, Sam A Gleason, Kelly Russo, Scott J Andrews, Simon Neve, Rachael Kennedy, Pamela J. Maze, Ian Dietz, David M. Allis, C. David Turecki, Gustavo Varga–Weisz, Patrick Tamminga, Carol Shen, Li Nestler, Eric J. |
author_facet | Sun, HaoSheng Damez–Werno, Diane M. Scobie, Kimberly N. Shao, Ning–Yi Dias, Caroline Rabkin, Jacqui Koo, Ja Wook Korb, Erica Bagot, Rosemary C. Ahn, Francisca H. Cahill, Michael E. Labonté, Benoit Mouzon, Ezekiell Heller, Elizabeth A. Cates, Hannah Golden, Sam A Gleason, Kelly Russo, Scott J Andrews, Simon Neve, Rachael Kennedy, Pamela J. Maze, Ian Dietz, David M. Allis, C. David Turecki, Gustavo Varga–Weisz, Patrick Tamminga, Carol Shen, Li Nestler, Eric J. |
author_sort | Sun, HaoSheng |
collection | PubMed |
description | Improved treatment for major depressive disorder (MDD) remains elusive due to limited understanding of its underlying biological mechanisms. Stress–induced maladaptive transcriptional regulation within limbic neural circuits likely contributes to the development of MDD, possibly through epigenetic factors that regulate chromatin structure. We establish that persistent upregulation of the ACF ATP–dependent chromatin remodeling complex, occurring in the nucleus accumbens of stress–susceptible mice and depressed humans, is necessary for stress–induced depressive–like behaviors. Altered ACF binding after chronic stress is correlated with altered nucleosome positioning, particularly around the transcription start sites of affected genes. These alterations in ACF binding and nucleosome positioning are associated with repressed expression of genes implicated in susceptibility to stress. Together, we identify the ACF chromatin remodeling complex as a critical component in the development of susceptibility to depression and in regulating stress–related behaviors. |
format | Online Article Text |
id | pubmed-4598281 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-45982812016-04-01 ACF chromatin remodeling complex mediates stress–induced depressive–like behavior Sun, HaoSheng Damez–Werno, Diane M. Scobie, Kimberly N. Shao, Ning–Yi Dias, Caroline Rabkin, Jacqui Koo, Ja Wook Korb, Erica Bagot, Rosemary C. Ahn, Francisca H. Cahill, Michael E. Labonté, Benoit Mouzon, Ezekiell Heller, Elizabeth A. Cates, Hannah Golden, Sam A Gleason, Kelly Russo, Scott J Andrews, Simon Neve, Rachael Kennedy, Pamela J. Maze, Ian Dietz, David M. Allis, C. David Turecki, Gustavo Varga–Weisz, Patrick Tamminga, Carol Shen, Li Nestler, Eric J. Nat Med Article Improved treatment for major depressive disorder (MDD) remains elusive due to limited understanding of its underlying biological mechanisms. Stress–induced maladaptive transcriptional regulation within limbic neural circuits likely contributes to the development of MDD, possibly through epigenetic factors that regulate chromatin structure. We establish that persistent upregulation of the ACF ATP–dependent chromatin remodeling complex, occurring in the nucleus accumbens of stress–susceptible mice and depressed humans, is necessary for stress–induced depressive–like behaviors. Altered ACF binding after chronic stress is correlated with altered nucleosome positioning, particularly around the transcription start sites of affected genes. These alterations in ACF binding and nucleosome positioning are associated with repressed expression of genes implicated in susceptibility to stress. Together, we identify the ACF chromatin remodeling complex as a critical component in the development of susceptibility to depression and in regulating stress–related behaviors. 2015-09-21 2015-10 /pmc/articles/PMC4598281/ /pubmed/26390241 http://dx.doi.org/10.1038/nm.3939 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Sun, HaoSheng Damez–Werno, Diane M. Scobie, Kimberly N. Shao, Ning–Yi Dias, Caroline Rabkin, Jacqui Koo, Ja Wook Korb, Erica Bagot, Rosemary C. Ahn, Francisca H. Cahill, Michael E. Labonté, Benoit Mouzon, Ezekiell Heller, Elizabeth A. Cates, Hannah Golden, Sam A Gleason, Kelly Russo, Scott J Andrews, Simon Neve, Rachael Kennedy, Pamela J. Maze, Ian Dietz, David M. Allis, C. David Turecki, Gustavo Varga–Weisz, Patrick Tamminga, Carol Shen, Li Nestler, Eric J. ACF chromatin remodeling complex mediates stress–induced depressive–like behavior |
title | ACF chromatin remodeling complex mediates stress–induced depressive–like behavior |
title_full | ACF chromatin remodeling complex mediates stress–induced depressive–like behavior |
title_fullStr | ACF chromatin remodeling complex mediates stress–induced depressive–like behavior |
title_full_unstemmed | ACF chromatin remodeling complex mediates stress–induced depressive–like behavior |
title_short | ACF chromatin remodeling complex mediates stress–induced depressive–like behavior |
title_sort | acf chromatin remodeling complex mediates stress–induced depressive–like behavior |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598281/ https://www.ncbi.nlm.nih.gov/pubmed/26390241 http://dx.doi.org/10.1038/nm.3939 |
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