Phosphorylation of Maf-family bZIP transcription factor NRL by Casein Kinase 2 modulates the expression of mammalian rod photoreceptor genes

Maf-family bZIP protein NRL specifies rod photoreceptor cell fate during retinal development and, in concert with homeodomain protein CRX and other transcription regulatory factors, controls the expression of several rod-specific genes, including Rhodopsin. Post-translational modifications, including phosphorylation, are shown to modulate the transcriptional regulatory activity of NRL. Here, we identify Casein Kinase 2 (CK2) in protein complexes bound to Rhodopsin promoter and enhancer regions and in NRL-enriched fractions from the bovine retina. We validate by co-immunoprecipitation that CK2 physically associates with NRL in developing and adult mouse retina. Furthermore, we present evidence that that CK2 potentially phosphorylates NRL at Ser117 residue and negatively controls NRL-mediated activation of Rhodopsin promoter in HEK293 cells. Overexpression of CK2 along with Rhodopsin promoter driving DsRed reporter gene in the mouse retina leads to a reduction in the reporter gene expression as well as altered expression of many NRL target genes. Our studies demonstrate fine-tuning of gene expression in rod photoreceptors by post-translational modifications of NRL.