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Social isolation stress induces ATF‐7 phosphorylation and impairs silencing of the 5‐HT 5B receptor gene
Author(s) -
Maekawa Toshio,
Kim Seungjoon,
Nakai Daisuke,
Makino Chieko,
Takagi Tsuyoshi,
Ogura Hiroo,
Yamada Kazuyuki,
Chatton Bruno,
Ishii Shunsuke
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2009.318
Subject(s) - biology , gene silencing , phosphorylation , microbiology and biotechnology , gene , receptor , genetics
Many symptoms induced by isolation rearing of rodents may be relevant to neuropsychiatric disorders, including depression. However, identities of transcription factors that regulate gene expression in response to chronic social isolation stress remain elusive. The transcription factor ATF‐7 is structurally related to ATF‐2, which is activated by various stresses, including inflammatory cytokines. Here, we report that Atf‐7 ‐deficient mice exhibit abnormal behaviours and increased 5‐HT receptor 5B ( Htr5b ) mRNA levels in the dorsal raphe nuclei. ATF‐7 silences the transcription of Htr5B by directly binding to its 5′‐regulatory region, and mediates histone H3‐K9 trimethylation via interaction with the ESET histone methyltransferase. Isolation‐reared wild‐type (WT) mice exhibit abnormal behaviours that resemble those of Atf‐7 ‐deficient mice. Upon social isolation stress, ATF‐7 in the dorsal raphe nucleus is phosphorylated via p38 and is released from the Htr5b promoter, leading to the upregulation of Htr5b . Thus, ATF‐7 may have a critical role in gene expression induced by social isolation stress.