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. Overall design: This study was performed on samples collected from Sprague Dawley rats (n=9 pooled). The hypothalamic supraoptic and paraventricular nucleus were collected by tissue punching from rats that underwent 72 hours of water deprivation. We performed Creb3l1 chromatin immunoprecipitation DNA-sequencing (ChIP-seq) in these magnocellular neurone (MCN) enriched hypothalamic samples to describe the Creb3l1 target transcriptome.