Three-dimensional genome restructuring across timescales of activity-induced neuronal gene expression.
Three-dimensional genome restructuring across timescales of activity-induced neuronal gene expression.
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DOI：
10.1038/s41593-020-0634-6
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发表时间：
2020-06
影响因子：
25
通讯作者：
Phillips-Cremins JE
中科院分区：
文献类型：
--
作者：
Beagan JA;Pastuzyn ED;Fernandez LR;Guo MH;Feng K;Titus KR;Chandrashekar H;Shepherd JD;Phillips-Cremins JE
神经元激活诱导即刻早期基因(IEGs)的快速转录和围绕次级反应基因(SRGs)的长期染色质重塑。在这里，我们使用高分辨率染色体构象捕获碳拷贝测序(5C-SEQ)来阐明在神经活动的短期和长期变化期间，长范围染色质环改变的程度。我们发现，在皮层神经元激活过程中，围绕特定IEGs、SRGs和突触基因的10%以上的环路是从头开始诱导的。IEG Fos和Arc通过刺激后20 分钟内形成的单一短程环路连接到活性依赖的增强子，在信使RNA水平达到峰值之前。相比之下，SRG BDNF既参与预先存在的环，也参与活性诱导的环，这些环在1-6 h内形成。我们还表明，与自闭症和精神分裂症相关的常见单核苷酸变体与不同类别的活性依赖环增强子共定位。我们的数据将结构复杂性与转录动力学联系起来，并揭示了在神经元刺激过程中高阶染色质结构重新配置的快速时间尺度。
Neuronal activation induces rapid transcription of immediate early genes (IEGs) and longer-term chromatin remodeling around secondary response genes (SRGs). Here, we use high-resolution chromosome-conformation-capture carbon-copy sequencing (5C-seq) to elucidate the extent to which long-range chromatin loops are altered during short- and long-term changes in neural activity. We find that more than 10% of loops surrounding select IEGs, SRGs, and synaptic genes are induced de novo during cortical neuron activation. IEGs Fos and Arc connect to activity-dependent enhancers via singular short-range loops that form within 20 min after stimulation, prior to peak messenger RNA levels. By contrast, the SRG Bdnf engages in both pre-existing and activity-inducible loops that form within 1–6 h. We also show that common single-nucleotide variants that are associated with autism and schizophrenia are colocalized with distinct classes of activity-dependent, looped enhancers. Our data link architectural complexity to transcriptional kinetics and reveal the rapid timescale by which higher-order chromatin architecture reconfigures during neuronal stimulation.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
30.8
作者：
Fulco, Charles P.;Nasser, Joseph;Engreitz, Jesse M.
通讯作者：
Engreitz, Jesse M.
影响因子：
7
作者：
Beagan JA;Duong MT;Titus KR;Zhou L;Cao Z;Ma J;Lachanski CV;Gillis DR;Phillips-Cremins JE
通讯作者：
Phillips-Cremins JE