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.
Mesh Terms:
DNA-Binding Proteins, Forkhead Transcription Factors, Gene Expression Regulation, Neoplastic, Humans, Immunoblotting, Jumonji Domain-Containing Histone Demethylases, Melanoma, Nerve Tissue Proteins, Nuclear Proteins, Oligonucleotide Array Sequence Analysis, PAX9 Transcription Factor, Polymerase Chain Reaction, Repressor Proteins, Skin Neoplasms, Transcription, Genetic, Tumor Suppressor Proteins
Int. J. Cancer
Date: Mar. 01, 2008
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