title: Social isolation stress induces ATF-7 phosphorylation and impairs silencing of the 5-HT 5B receptor gene.
abstract: 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.
authors.affiliation: Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, Tsukuba, Ibaraki, Japan. maekawa@rtc.riken.jp
authors.forename: Toshio
authors.initials: T
authors.lastname: Maekawa
authors.forename: Seungjoon
authors.initials: S
authors.lastname: Kim
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakai
authors.forename: Chieko
authors.initials: C
authors.lastname: Makino
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takagi
authors.forename: Hiroo
authors.initials: H
authors.lastname: Ogura
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Yamada
authors.forename: Bruno
authors.initials: B
authors.lastname: Chatton
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ishii
mesh_terms: D051698:Activating Transcription Factor 2 / Q000378:metabolism; D051696:Activating Transcription Factors / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D015870:Gene Expression; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism; D011985:Receptors, Serotonin / Q000235:genetics*; D012919:Social Behavior; D012934:Social Isolation; D013315:Stress, Psychological
chemical_list: D051698:Activating Transcription Factor 2; D051696:Activating Transcription Factors; C497106:Atf2 protein, mouse; D006657:Histones; D012333:RNA, Messenger; D011985:Receptors, Serotonin; C078730:serotonin 5 receptor