Social isolation stress induces ATF-7 phosphorylation and impairs silencing of the 5-HT 5B receptor gene
Social isolation stress induces ATF-7 phosphorylation and impairs silencing of the 5-HT 5B receptor gene
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DOI：
10.1038/emboj.2009.318
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发表时间：
2010-01-06
期刊：
影响因子：
11.4
通讯作者：
Ishii, Shunsuke
中科院分区：
文献类型：
--
作者：
Maekawa, Toshio;Kim, Seungjoon;Ishii, Shunsuke
啮齿动物隔离饲养引起的许多症状可能与神经精神疾病有关，包括抑郁症。然而，身份的转录因子，调节基因表达的慢性社会隔离压力仍然难以捉摸。转录因子ATF-7在结构上与ATF-2相关，ATF-2被各种应激激活，包括炎性细胞因子。在这里，我们报告，Atf-7缺陷小鼠表现出异常的行为和增加5-HT受体5 B（Htr 5 b）的中缝背核mRNA水平。ATF-7通过直接结合Htr 5 B的5 '调控区使其转录沉默，并通过与ESET组蛋白甲基转移酶相互作用介导组蛋白H3-K9三甲基化。隔离饲养的野生型（WT）小鼠表现出异常行为，类似于Atf-7缺陷小鼠。在社会隔离应激时，中缝背核中的ATF-7通过p38磷酸化并从Htr 5 b启动子释放，导致Htr 5 b上调。因此，ATF-7可能在社会隔离应激诱导的基因表达中起关键作用。The EMBO Journal（2010）29，184-195. doi：10.1038/doj.2009.318; 2009年11月5日在线发布
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. The EMBO Journal (2010) 29, 184-195. doi: 10.1038/emboj.2009.318; Published online 5 November 2009