Genomic regions occupied by both RARa and VDR are involved in the convergence and cooperation of retinoid and vitamin D signaling pathways.

In this study, the retinoid and vitamin D pathways were investigated in PMA-differentiated THP-1 cells treated with or without the RARa agonist, AM580, and/or the VDR agonist, 1,25-dihydroxyvitamin D3 (1,25-vitD or calcitriol), using global approaches. Binding regions of RARa and VDR were determined in PMA-differentiated THP-1 cells using chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq). The gene sets regulated by AM580 and/or 1,25-vitD were identified by RNA-sequencing (RNA-seq). The activity of the regulatory regions was determined by MED1 (a subunit of the Mediator complex) ChIP-seq and chromatin openness was measured using assay for transposase-accessible chromatin with sequencing (ATAC-seq). Overall design: THP-1 cells were stimulated with 20 nM PMA for 16 hours. PMA-differentiated THP-1 cells were treated with vehicle (DMSO:EtOH) or 100 nM AM580 for 1 hour. Two replicates for each treatment condition were analyzed for ATAC-seq.