Dataset Information

Hypothalamic protein profiling from mice subjected to social defeat stress

ABSTRACT: We have analysed changes in the hypothalamus using iTRAQ proteomics 4 plex from mice exposed to social defeat protocol using Qexactive and Orbitrap Velos

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Shiladitya Mitra

LAB HEAD: Suman Thakur

PROVIDER: PXD005644 | Pride | 2024-05-28

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	SOCIAL_DEFEAT_SCX_ORBITRAP_RUN_ALL_RAW_FILES_TOGETHER.msf	Msf
	SOCIAL_DEFEAT_SCX_ORBITRAP_RUN_ALL_RAW_FILES_TOGETHER_PEP.pep.pep.pep.xml	Pepxml
	SOCIAL_DEFEAT_SCX_ORBITRAP_RUN_ALL_RAW_FILES_TOGETHER_PEPTIDE.xls	Xls
	SOCIAL_DEFEAT_SCX_ORBITRAP_RUN_ALL_RAW_FILES_TOGETHER_PROT.prot.prot.xml	Xml
	SOCIAL_DEFEAT_SCX_ORBITRAP_RUN_ALL_RAW_FILES_TOGETHER_PROTEINS.xls	Xls

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Project description: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. 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.

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Hypothalamic protein profiling from mice subjected to social defeat stress

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