Cohesin-dependence of neuronal gene expression relates to chromatin loop length.
Cohesin-dependence of neuronal gene expression relates to chromatin loop length.
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DOI：
10.7554/elife.76539
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发表时间：
2022-04-26
期刊：
影响因子：
7.7
通讯作者：
Merkenschlager M
中科院分区：
文献类型：
--
作者：
Calderon L;Weiss FD;Beagan JA;Oliveira MS;Georgieva R;Wang YF;Carroll TS;Dharmalingam G;Gong W;Tossell K;de Paola V;Whilding C;Ungless MA;Fisher AG;Phillips-Cremins JE;Merkenschlager M
Cohesin和CTCF是3D基因组组织的主要驱动因素，但它们在神经元中的作用仍在显现。在这里，我们显示了一个突出的作用，促进神经元的成熟和稳态的基因表达的粘附素。出乎意料的是，我们观察到两个主要类别的活性调节基因，在小鼠原代皮层神经元中具有明显的依赖性。立即早期基因（IEGs）仍然完全可诱导的KCl和BDNF，和短程增强子-启动子接触在IEGs Fos的形成鲁棒性的情况下的粘附素。与此相反，粘着蛋白是需要充分表达的一个子集的第二个反应基因的特点是长距离染色质接触。在突触传递和神经递质信号传导中具有关键功能的组成性神经元基因的粘着蛋白依赖性也与染色质环长度成比例。我们的数据表明，初级皮质神经元的成熟和激活所需的关键基因依赖于粘着蛋白的充分表达，以及这些基因依赖于粘着蛋白的程度与它们的染色质接触所穿越的基因组距离有关。
Cohesin and CTCF are major drivers of 3D genome organization, but their role in neurons is still emerging. Here, we show a prominent role for cohesin in the expression of genes that facilitate neuronal maturation and homeostasis. Unexpectedly, we observed two major classes of activity-regulated genes with distinct reliance on cohesin in mouse primary cortical neurons. Immediate early genes (IEGs) remained fully inducible by KCl and BDNF, and short-range enhancer-promoter contacts at the IEGs Fos formed robustly in the absence of cohesin. In contrast, cohesin was required for full expression of a subset of secondary response genes characterized by long-range chromatin contacts. Cohesin-dependence of constitutive neuronal genes with key functions in synaptic transmission and neurotransmitter signaling also scaled with chromatin loop length. Our data demonstrate that key genes required for the maturation and activation of primary cortical neurons depend on cohesin for their full expression, and that the degree to which these genes rely on cohesin scales with the genomic distance traversed by their chromatin contacts.