title: ACF chromatin-remodeling complex mediates stress-induced depressive-like behavior.
abstract: Improved treatment for major depressive disorder (MDD) remains elusive because of the limited understanding of its underlying biological mechanisms. It is likely that stress-induced maladaptive transcriptional regulation in limbic neural circuits contributes to the development of MDD, possibly through epigenetic factors that regulate chromatin structure. We establish that persistent upregulation of the ACF (ATP-utilizing chromatin assembly and remodeling factor) 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. We found that altered ACF binding after chronic stress was correlated with altered nucleosome positioning, particularly around the transcription start sites of affected genes. These alterations in ACF binding and nucleosome positioning were associated with repressed expression of genes implicated in susceptibility to stress. Together, our findings identify the ACF chromatin-remodeling complex as a critical component in the development of susceptibility to depression and in regulating stress-related behaviors.
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: HaoSheng
authors.initials: H
authors.lastname: Sun
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Damez-Werno
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Kimberly N
authors.initials: KN
authors.lastname: Scobie
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Ning-Yi
authors.initials: NY
authors.lastname: Shao
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Dias
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Jacqui
authors.initials: J
authors.lastname: Rabkin
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Ja Wook
authors.initials: JW
authors.lastname: Koo
authors.affiliation: Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Korb
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Rosemary C
authors.initials: RC
authors.lastname: Bagot
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Francisca H
authors.initials: FH
authors.lastname: Ahn
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cahill
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Benoit
authors.initials: B
authors.lastname: Labonté
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Ezekiell
authors.initials: E
authors.lastname: Mouzon
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Heller
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Cates
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Sam A
authors.identifier: http://orcid.org/0000-0002-2104-2272
authors.initials: SA
authors.lastname: Golden
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Gleason
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Russo
authors.affiliation: The Babraham Institute, Cambridge, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Andrews
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Rachael
authors.initials: R
authors.lastname: Neve
authors.affiliation: Department of Psychology, University of California Los Angeles, Los Angeles, California, USA.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Kennedy
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York, USA.|Department of Pharmacology and System Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Maze
authors.affiliation: Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, New York, USA.|Institute on Addictions, University at Buffalo, Buffalo, New York, USA.
authors.forename: David M
authors.identifier: http://orcid.org/0000-0002-6927-9236
authors.initials: DM
authors.lastname: Dietz
authors.affiliation: Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York, USA.
authors.forename: C David
authors.initials: CD
authors.lastname: Allis
authors.affiliation: Department of Psychiatry, McGill University, Montreal, Québec, Canada.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
authors.affiliation: The Babraham Institute, Cambridge, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Varga-Weisz
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Tamminga
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
mesh_terms: D000818:Animals; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone; D003863:Depression / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013315:Stress, Psychological; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D000092468:Bromodomain Containing Proteins
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D014157:Transcription Factors; C492319:BAZ1A protein, human; D000092468:Bromodomain Containing Proteins