Regulation of RelB expression during the initiation of dendritic cell differentiation

The transcription factor ROB is required for proper development and function of dendritic cells (DCs), and its expression is upregulated early during differentiation from a variety of progenitors. We explored this mechanism of upregulation in the KG1 cell line model of a DC progenitor and in the differentiation-resistant KG1a subline. ROB expression is relatively higher in untreated KG1a cells but is upregulated only during differentiation of KG1 by an early enhancement of transcriptional elongation, followed by an increase in transcription initiation. Restoration of protein kinase C beta II (PKC beta II) expression in KG1a cells allows them to differentiate into DCs. We show that PKC beta II also downregulated constitutive expression of NF-kappa B in KG1a-transfected cells and restores the upregulation of ROB during differentiation by increased transcriptional initiation and elongation. The two mechanisms are independent and sensitive to PKC signaling levels. Conversely, RelB upregulation was inhibited in primary human monocytes where PKC beta II expression was knocked down by small interfering RNA targeting. Altogether, the data show that ROB expression during DC differentiation is controlled by PKC beta II-mediated regulation of transcriptional initiation and elongation.