Transcription factor Creb3l1 maintains proteostasis in neuroendocrine cells [ChiP-seq]

We have shown that the expression of the endoplasmic reticulum stress sensor Creb3l1 increases in magnocellular neurones (MCNs) in the rat hypothalamus in response to increased physiological demands for protein synthesis. Here we adopted a multiomic strategy to investigate specific roles of Creb3l1 in MCN homeostasis. We first performed chromatin immunoprecipitation followed by genome sequencing (ChIP-seq) to identify Creb3l1 genomic targets in the water deprived MCN enriched hypothalamic preparation. We then compared ChIP-seq gene targets with water deprived and Creb3l1 knockdown supraoptic nucleus RNA sequencing transcriptome datasets. This has provided an integrated signalling-gene regulation network for this transcription factor illuminating changes to cell pathways and function, an approach that has led us to understand the physiological changes that occur in MCNs to cope with excessive protein demands.我们已证实，内质网应激感受器Creb3l1在大鼠下丘脑的大细胞神经元（magnocellular neurones，缩写MCNs）中的表达，会因蛋白质合成的生理需求升高而上调。本研究采用多组学策略，探究Creb3l1在MCN稳态维持中的特定作用。我们首先通过染色质免疫共沉淀结合基因组测序（ChIP-seq），在饮水剥夺的、富集MCNs的下丘脑制备物中鉴定Creb3l1的基因组靶标。随后，我们将ChIP-seq鉴定得到的基因靶标，与饮水剥夺且Creb3l1敲低的视上核RNA测序转录组数据集进行对比分析。上述工作构建了该转录因子的整合信号传导-基因调控网络，阐明了细胞通路与功能的改变；通过这一研究策略，我们得以解析MCNs为应对过量蛋白质合成需求所发生的生理变化。