Cold inducible genes and promoters in Chinese Hamster Ovary cells were identified by analyzing transcriptome data of cultivation before and after temperature shift from 37 to 33°C

Lower cultivation temperature dramatically affects cell growth and cellular productivity in CHO and is often used in industrial applications with the aim to enhance productivity. Cold-inducible proteins whose activity is induced at lower temperature play an important role in understanding the mechanisms of cold-induced changes in gene expression under cold-stress. One of these mechanisms is increased transcription of specific target genes via elements in the promoter region named cold-inducible promoters. This study provides a list of cold-inducible genes and endogenous cold-inducible promoters derived from CHO cells. Transcriptome data during temperature-shift cultivation from 37 to 33°C was analyzed to identify 94 cold-inducible genes, which are highly expressed and have a high fold change in expression after the temperature-shift. In addition, different cold-inducible promoters were identified from the top 10 cold-inducible genes, that showed up to 11-fold increased luciferase expression at lowered temperature in transient application. Therefore, the identified CHO cold-inducible promoters might support future studies associated with inducible systems in regulation of gene expression. Additionally, several common transcription factor binding sites have been identified in the top cold-inducible promoter sequences and expression of their corresponding transcription factors over temperature-shift cultivation was evaluated. These might be responsible for enhanced promoter activity under lower temperature and can be used as engineering targets.