RBP2‐H1/JARID1B is a transcriptional regulator with a tumor suppressive potential in melanoma cells

The RBP2‐H1/JARID1B nuclear protein belongs to the ARID family of DNA‐binding proteins and is a potential tumor suppressor that is lost during melanoma development. As we have recently shown, one physiological function of RBP2‐H1/JARID1B is to exert cell cycle control via maintenance of active retinoblastoma protein. We now add new evidence that RBP2‐H1/JARID1B can also directly regulate gene transcription in a reporter assay system, either alone or as part of a multimolecular complex together with the developmental transcription factors FOXG1b and PAX9. In melanoma cells, chromatin immunoprecipitation combined with promoter chip analysis (ChIP‐on‐chip) suggests a direct binding of re‐expressed RBP2‐H1/JARID1B to a multitude of human regulatory chromosomal elements (promoters, enhancers and introns). Among those, a set of 23 genes, including the melanoma relevant genes CDK6 and JAG‐1 could be confirmed by cDNA microarray analyses to be differentially expressed after RBP2‐H1/JARID1B re‐expression. In contrast, in nonmelanoma HEK 293 cells, RBP2‐H1/JARID1B overexpression only evokes a minor transcriptional response in cDNA microarray analyses. Because the transcriptional regulation in melanoma cells is accompanied by an inhibition of proliferation, an increase in caspase activity and a partial cell cycle arrest in G1/0, our data support an anti‐tumorigenic role of RBP2‐H1/JARID1B in melanocytic cells. © 2007 Wiley‐Liss, Inc.