Gad2的转录调控
Transcriptional control of Gad2.
作者信息
Pan Zhizhong Z
机构信息
Department of Anesthesiology and Pain Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
出版信息
Transcription. 2012 Mar-Apr;3(2):68-72. doi: 10.4161/trns.19511. Epub 2012 Mar 1.
Abstract
Gad2 encodes GAD65, which is present preferentially in presynaptic terminals for synthesis of GABA for vesicle release. Gad2 is a regulatory target of cell activities in various brain functions and in GABA perturbation-related neurological diseases. However, our understanding of how Gad2 is transcriptionally regulated and how Gad2 transcription responds to changing cell environment under these conditions is still limited. This review discusses recent advances in the regulatory mechanisms for Gad2 transcription and highlights the characteristics of TATA-less Gad2 promoters and regulation of Gad2 transcription by CREB and by activity-dependent epigenetic modification of the chromatin structure in regulatory elements of the Gad2 gene.
摘要
Gad2编码GAD65，GAD65优先存在于突触前终末，用于合成γ-氨基丁酸（GABA）以供囊泡释放。Gad2是各种脑功能以及与GABA紊乱相关的神经疾病中细胞活动的调控靶点。然而，我们对Gad2转录调控的方式以及在这些情况下Gad2转录如何响应不断变化的细胞环境的了解仍然有限。本文综述讨论了Gad2转录调控机制的最新进展，并强调了无TATA框的Gad2启动子的特征，以及CREB对Gad2转录的调控，以及Gad2基因调控元件中染色质结构的活性依赖性表观遗传修饰对Gad2转录的调控。
相似文献
1
Transcriptional control of Gad2.Gad2的转录调控
Transcription. 2012 Mar-Apr;3(2):68-72. doi: 10.4161/trns.19511. Epub 2012 Mar 1.
2
Rats deficient in the GAD65 isoform exhibit epilepsy and premature lethality.GAD65 同工型缺乏的大鼠表现出癫痫和过早死亡。
FASEB J. 2021 Feb;35(2):e21224. doi: 10.1096/fj.202001935R. Epub 2020 Nov 25.
3
Epigenetic suppression of GAD65 expression mediates persistent pain.表观遗传抑制 GAD65 表达介导持续性疼痛。
Nat Med. 2011 Oct 9;17(11):1448-55. doi: 10.1038/nm.2442.
4
GABAergic Interneuron Differentiation in the Basal Forebrain Is Mediated through Direct Regulation of Glutamic Acid Decarboxylase Isoforms by Homeobox Transcription Factors.基底前脑中γ-氨基丁酸能中间神经元的分化是通过同源框转录因子对谷氨酸脱羧酶亚型的直接调控来介导的。
J Neurosci. 2017 Sep 6;37(36):8816-8829. doi: 10.1523/JNEUROSCI.2125-16.2017. Epub 2017 Aug 8.
5
Genetic manipulation of the γ-aminobutyric acid (GABA) shunt in rice: overexpression of truncated glutamate decarboxylase (GAD2) and knockdown of γ-aminobutyric acid transaminase (GABA-T) lead to sustained and high levels of GABA accumulation in rice kernels.对水稻γ-氨基丁酸（GABA）分流的遗传操作：截短谷氨酸脱羧酶（GAD2）的过表达和γ-氨基丁酸转氨酶（GABA-T）的敲低导致水稻籽粒中 GABA 积累持续且高水平。
Plant Biotechnol J. 2013 Jun;11(5):594-604. doi: 10.1111/pbi.12050. Epub 2013 Feb 20.
6
Maternal immune activation induces GAD1 and GAD2 promoter remodeling in the offspring prefrontal cortex.母体免疫激活诱导后代前额叶皮层中 GAD1 和 GAD2 启动子重塑。
Epigenetics. 2015;10(12):1143-55. doi: 10.1080/15592294.2015.1114202.
7
GAD2 on chromosome 10p12 is a candidate gene for human obesity.位于10号染色体p12区域的GAD2基因是人类肥胖症的候选基因。
PLoS Biol. 2003 Dec;1(3):E68. doi: 10.1371/journal.pbio.0000068. Epub 2003 Nov 3.
8
Visualization of two distinct classes of neurons by gad2 and zic1 promoter/enhancer elements in the dorsal hindbrain of developing zebrafish reveals neuronal connectivity related to the auditory and lateral line systems.通过gad2和zic1启动子/增强子元件对发育中斑马鱼后脑背侧的两类不同神经元进行可视化，揭示了与听觉和侧线系统相关的神经元连接。
Dev Dyn. 2007 Mar;236(3):706-18. doi: 10.1002/dvdy.21084.
9
Brainstem brain-derived neurotrophic factor signaling is required for histone deacetylase inhibitor-induced pain relief.组蛋白去乙酰化酶抑制剂诱导的疼痛缓解需要脑干脑源性神经营养因子信号传导。
Mol Pharmacol. 2015 Jun;87(6):1035-41. doi: 10.1124/mol.115.098186. Epub 2015 Apr 7.
10
GAD65 Promoter Polymorphism rs2236418 Modulates Harm Avoidance in Women via Inhibition/Excitation Balance in the Rostral ACC.GAD65 启动子多态性 rs2236418 通过调节额前皮质腹侧部的抑制/兴奋平衡来调节女性的回避倾向。
J Neurosci. 2018 May 30;38(22):5067-5077. doi: 10.1523/JNEUROSCI.1985-17.2018. Epub 2018 May 3.
引用本文的文献
1
Deconvolution-Based Transcriptomic Analysis in the Hippocampus Reveals Cell Type-Specific Risk Genes and Pathways Associated With Depression and Suicide.基于去卷积的海马体转录组分析揭示了与抑郁症和自杀相关的细胞类型特异性风险基因和通路。
Biol Psychiatry Glob Open Sci. 2025 May 8;5(5):100530. doi: 10.1016/j.bpsgos.2025.100530. eCollection 2025 Sep.
2
CellSP: Module discovery and visualization for subcellular spatial transcriptomics data.CellSP：用于亚细胞空间转录组学数据的模块发现与可视化
bioRxiv. 2025 Apr 18:2025.01.12.632553. doi: 10.1101/2025.01.12.632553.
3
Unveiling microbial dynamics in terasi spontaneous fermentation: Insights into glutamate and GABA production.揭示特拉萨自然发酵过程中的微生物动态：对谷氨酸和γ-氨基丁酸产生的见解。
Curr Res Food Sci. 2024 Dec 9;10:100950. doi: 10.1016/j.crfs.2024.100950. eCollection 2025.
4
Upregulated spinal histone deacetylases induce nociceptive sensitization by inhibiting the GABA system in chronic constriction injury-induced neuropathy in rats.脊髓中上调的组蛋白去乙酰化酶通过抑制慢性缩窄性损伤诱导的大鼠神经病变中的γ-氨基丁酸（GABA）系统来诱导伤害性敏感化。
Pain Rep. 2024 Nov 6;9(6):e1209. doi: 10.1097/PR9.0000000000001209. eCollection 2024 Dec.
5
Citalopram exposure of hESCs during neuronal differentiation identifies dysregulated genes involved in neurodevelopment and depression.在神经元分化过程中，人胚胎干细胞暴露于西酞普兰可鉴定出参与神经发育和抑郁症的失调基因。
Front Cell Dev Biol. 2024 Jul 11;12:1428538. doi: 10.3389/fcell.2024.1428538. eCollection 2024.
6
RNA velocity prediction via neural ordinary differential equation.通过神经常微分方程进行RNA速度预测。
iScience. 2024 Mar 28;27(4):109635. doi: 10.1016/j.isci.2024.109635. eCollection 2024 Apr 19.
7
Irradiation and lithium treatment alter the global DNA methylation pattern and gene expression underlying a shift from gliogenesis towards neurogenesis in human neural progenitors.辐射和锂处理改变了人类神经祖细胞中从神经发生到神经发生的全局 DNA 甲基化模式和基因表达。
Transl Psychiatry. 2023 Jul 13;13(1):258. doi: 10.1038/s41398-023-02560-w.
8
GABA facilitates spike propagation through branch points of sensory axons in the spinal cord.GABA 促进脊髓感觉轴突分支点的尖峰传播。
Nat Neurosci. 2022 Oct;25(10):1288-1299. doi: 10.1038/s41593-022-01162-x. Epub 2022 Sep 26.
9
Pax6 limits the competence of developing cerebral cortical cells to respond to inductive intercellular signals.Pax6 限制了发育中的大脑皮层细胞对诱导性细胞间信号做出反应的能力。
PLoS Biol. 2022 Sep 6;20(9):e3001563. doi: 10.1371/journal.pbio.3001563. eCollection 2022 Sep.
10
A role of anterior cingulate cortex in the emergence of worker-parasite relationship.前扣带皮层在工蜂-寄生虫关系出现中的作用。
Proc Natl Acad Sci U S A. 2021 Nov 30;118(48). doi: 10.1073/pnas.2111145118.
本文引用的文献
1
Epigenetic suppression of GAD65 expression mediates persistent pain.表观遗传抑制 GAD65 表达介导持续性疼痛。
Nat Med. 2011 Oct 9;17(11):1448-55. doi: 10.1038/nm.2442.
2
A decade of exploring the cancer epigenome - biological and translational implications.一个探索癌症表观基因组的十年 - 生物学和转化意义。
Nat Rev Cancer. 2011 Sep 23;11(10):726-34. doi: 10.1038/nrc3130.
3
Beyond classical benzodiazepines: novel therapeutic potential of GABAA receptor subtypes.超越经典苯二氮䓬类药物：GABAA 受体亚型的新治疗潜力。
Nat Rev Drug Discov. 2011 Jul 29;10(9):685-97. doi: 10.1038/nrd3502.
4
Epigenetic regulation of gene expression in physiological and pathological brain processes.生理和病理脑过程中基因表达的表观遗传调控。
Physiol Rev. 2011 Apr;91(2):603-49. doi: 10.1152/physrev.00012.2010.
5
Enhancer function: new insights into the regulation of tissue-specific gene expression.增强子功能：组织特异性基因表达调控的新见解。
Nat Rev Genet. 2011 Apr;12(4):283-93. doi: 10.1038/nrg2957. Epub 2011 Mar 1.
6
CREB-Dependent Regulation of GAD65 Transcription by BDNF/TrkB in Cortical Interneurons.CREB 依赖性调控皮层中间神经元中 BDNF/TrkB 对 GAD65 的转录。
Cereb Cortex. 2011 Apr;21(4):777-88. doi: 10.1093/cercor/bhq150. Epub 2010 Aug 25.
7
Sustained stress-induced changes in mice as a model for chronic depression.应激诱导的慢性抑郁模型中小鼠的持续变化。
Psychopharmacology (Berl). 2010 Jun;210(3):393-406. doi: 10.1007/s00213-010-1835-6. Epub 2010 Apr 20.
8
Widespread transcription at neuronal activity-regulated enhancers.神经元活动调节增强子的广泛转录。
Nature. 2010 May 13;465(7295):182-7. doi: 10.1038/nature09033. Epub 2010 Apr 14.
9
Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies.神经疾病中的表观遗传机制：基因、综合征与治疗
Lancet Neurol. 2009 Nov;8(11):1056-72. doi: 10.1016/S1474-4422(09)70262-5.
10
Stringent specificity in the construction of a GABAergic presynaptic inhibitory circuit.γ-氨基丁酸能突触前抑制性回路构建中的严格特异性
Cell. 2009 Oct 2;139(1):161-74. doi: 10.1016/j.cell.2009.08.027.
Zotero 插件