Gene expression changes in pancreatic α-cell lines following knock-out Of either CK2α or CK2α'

Abstract

Background Protein kinase CK2 is known to exist as a tetramer of two catalytic α- or α’- subunits and two non-catalytic β-subunits, or as multimers of this tetramer. Moreover, CK2α (CSNK2A1) and CK2α’ (CSNK2A2) are also active in the absence of CK2β (CSNK2B). Very little is known about specific functions of the individual subunits of protein kinase CK2.

Results In order to study the effects of CK2α and CK2α’ on gene expression, we used the Mus musculus pancreatic α-cell line αTC1 and two derivatives with either CK2α (KO1 cells) or CK2α’ (KO2 cells) expression knocked-out by CRISPR/Cas technology. We found numerous genes deregulated in both KO1 and KO2 cells compared to the parental cells. Applying stringent thresholds, 266 genes were found down-regulated and 153 genes up-regulated in KO1 cells, 233 genes were found down-regulated and 84 genes up-regulated in KO2 cells. Dozens of genes were found deregulated in a similar fashion in both KO1 and KO2 cells. We found altered expression of genes involved in the differentiation of pancreatic cells, including Hox genes, and in the regulation of glucagon synthesis or secretion. Moreover, many of the deregulated genes play an important role in developmental processes and in neuronal cell biology.

Conclusion Our findings reveal individual and shared functions of the CK2α and CK2α’ catalytic subunits, in particular regarding their involvement in regulating gene expression.