Identification of activity-induced Egr3-dependent genes reveals genes associated with DNA damage response and schizophrenia.
Identification of activity-induced Egr3-dependent genes reveals genes associated with DNA damage response and schizophrenia.
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DOI：
10.1038/s41398-022-02069-8
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发表时间：
2022-08-08
影响因子：
6.8
通讯作者：
Gallitano, Amelia L.
中科院分区：
文献类型：
--
作者：
Marballi, Ketan K.;Alganem, Khaled;Brunwasser, Samuel J.;Barkatullah, Arhem;Meyers, Kimberly T.;Campbell, Janet M.;Ozols, Annika B.;Mccullumsmith, Robert E.;Gallitano, Amelia L.
生物信息学和网络研究已经确定了立即早期基因转录因子早期生长反应3（EGR 3）作为一个主调节基因的差异表达的神经精神疾病患者的大脑从精神分裂症和双相情感障碍阿尔茨海默氏病。然而，很少有研究已经确定和验证哺乳动物大脑中的Egr 3依赖基因。我们之前已经证明Egr 3是小鼠应激反应行为，记忆和海马长期抑郁所必需的。为了鉴定可能调节这些过程的Egr 3依赖性基因，我们在电惊厥发作（ECS）后对野生型（WT）和Egr 3 −/−小鼠的Egr campi进行了表达微阵列，ECS是一种诱导包括Egr 3在内的立即早期基因最大表达的刺激。我们确定了69个基因在ECS后1小时在WT和Egr 3 −/−小鼠之间差异表达。生物信息学分析表明，其中许多基因在精神分裂症中发生改变或与精神分裂症相关，包括Mef 2c和Calb 2。Enrichr途径分析显示GADD 45（growth arrest and DNA-damage-inducible）家族（Gadd 45 b、Gadd 45 g）是差异表达基因的主要群体。与AP-1转录因子家族基因（Fos，Fosb）和着丝粒组织蛋白Cenpa中的差异表达基因一起，这些结果表明Egr 3是参与DNA损伤反应的基因的活性依赖性表达所必需的。我们的研究结果表明，EGR 3是关键的表达基因的错误表达在精神分裂症，并揭示了一个新的要求EGR 3在参与活动诱导的DNA损伤反应的基因的表达。
Bioinformatics and network studies have identified the immediate early gene transcription factor early growth response 3 (EGR3) as a master regulator of genes differentially expressed in the brains of patients with neuropsychiatric illnesses ranging from schizophrenia and bipolar disorder to Alzheimer’s disease. However, few studies have identified and validated Egr3-dependent genes in the mammalian brain. We have previously shown that Egr3 is required for stress-responsive behavior, memory, and hippocampal long-term depression in mice. To identify Egr3-dependent genes that may regulate these processes, we conducted an expression microarray on hippocampi from wildtype (WT) and Egr3−/− mice following electroconvulsive seizure (ECS), a stimulus that induces maximal expression of immediate early genes including Egr3. We identified 69 genes that were differentially expressed between WT and Egr3−/− mice one hour following ECS. Bioinformatic analyses showed that many of these are altered in, or associated with, schizophrenia, including Mef2c and Calb2. Enrichr pathway analysis revealed the GADD45 (growth arrest and DNA-damage-inducible) family (Gadd45b, Gadd45g) as a leading group of differentially expressed genes. Together with differentially expressed genes in the AP-1 transcription factor family genes (Fos, Fosb), and the centromere organization protein Cenpa, these results revealed that Egr3 is required for activity-dependent expression of genes involved in the DNA damage response. Our findings show that EGR3 is critical for the expression of genes that are mis-expressed in schizophrenia and reveal a novel requirement for EGR3 in the expression of genes involved in activity-induced DNA damage response.
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DOI：
10.1111/j.1365-2613.2010.00734.x
发表时间：
2010-12-01
影响因子：
3
作者：
Barry, Sean P.;Townsend, Paul A.;Stephanou, Anastasis
通讯作者：
Stephanou, Anastasis
影响因子：
3.4
作者：
Gurden, H;Schiffmann, SN;Schurmans, S
通讯作者：
Schurmans, S
影响因子：
3.3
作者：
Gallitano-Mendel, A.;Izumi, Y.;Milbrandt, J.
通讯作者：
Milbrandt, J.
影响因子：
8
作者：
Jin, SQ;Mazzacurati, L;Zhan, QM
通讯作者：
Zhan, QM
影响因子：
64.8
作者：
Barreto, Guillermo;Schaefer, Andrea;Niehrs, Christof
通讯作者：
Niehrs, Christof