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Series GSE54263 Query DataSets for GSE54263
Status Public on Sep 21, 2015
Title ACF chromatin remodeling complex mediates stress-induced depressive-like behavior through nucleosome repositioning and transcriptional regulation.
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Despite depression being one of the most prevalent and debilitating disorders worldwide, it has been difficult to understand its pathophysiology and to develop more effective treatments. Maladaptive transcriptional regulation within limbic neural circuits, including reward processing regions such as the nucleus accumbens (NAc), in response to chronic stress is thought to be a major contributor to the development of the syndrome. Epigenetic events?in particular, histone writers and erasers?that alter chromatin structure to regulate programs of gene expression have increasingly been associated with depression-related behavioral abnormalities in animal models and in depressed humans examined postmortem. However, very little is known about the ATP-dependent chromatin remodelers that control nucleosome positioning and the packing state of chromatin. Here we show that the ACF complex, part of the ISWI family of chromatin remodelers, is persistently and selectively upregulated in the NAc of mice that are susceptible to chronic social stress, as well as in the NAc of depressed human. We further establish that ACF induction is both necessary and sufficient for susceptibility to stress-induced depressive-like behaviors. Using ChIP-seq, we demonstrate that altered ACF binding after chronic stress is strongly correlated with altered nucleosome positioning, in particular, around the transcriptional start sites of affected genes. These alterations in ACF binding and nucleosome repositioning are associated with repressed expression of a subset of genes in animals that are susceptible to chronic stress. Together, these findings establish that active ATP-dependent chromatin remodeling by the ACF complex is a key regulator in the repression of genes that mediate susceptibility to social stress, and provide novel candidate targets for improved therapeutics of depression and other stress-related disorders.
Overall design c57bl/6 mice underwent chronic social defeat stress (CSDS), and social interaction test was used to separate animals into control, susceptible and resilient groups. Nucleus accumbens (NAc) tissue was collected 48 hours after the last defeat session, and then Acf1, SNF2H ChIP-seq or H3 MNase-seq were performed based on the control, susceptible, and resilient groups. Three sequencing replicates were performed on each group.
Contributor(s) Sun H, Shao N, Shen L, Nestler E
Citation(s) 26390241
Submission date Jan 21, 2014
Last update date May 15, 2019
Contact name Eric Nestler
Organization name Ichan School of Medicine at Mount Sinai
Street address 1425 Madison Avenue
City New York
State/province NY
ZIP/Postal code 10029
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (15)
GSM1311258 Con1_input
GSM1311259 Con_SNF2H
GSM1311260 Res1_input
BioProject PRJNA236060
SRA SRP035569

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Supplementary file Size Download File type/resource
GSE54263_RAW.tar 7.4 Gb (http)(custom) TAR (of BED, TDF, WIG)
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Raw data are available in SRA
Processed data provided as supplementary file

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