CONTEXT AND OBJECTIVE: Epigenetic dysregulation is implicated in pituitary 
neoplasia as the cause of silencing of several tumor suppressor genes. However, 
the upstream mediators of such events remain unknown.
DESIGN: We examined the three members of the DNA methyltransferase (DNMT) enzyme 
family in normal and neoplastic human and mouse pituitary cells.
SETTING: This study was performed at a university-affiliated cancer research 
institute.
MAIN OUTCOME MEASURES: Gene expression, promoter DNA methylation, histone 
modifications, and cell proliferation were determined.
RESULTS: In contrast to DNMT1 and DNMT3a, DNMT3b was expressed at relatively 
higher levels in neoplastic pituitary cells. However, examination of the human 
DNMT3b 5' region showed uniformly low DNA methylation levels with little 
difference between normal and tumor samples. Through pharmacological methylation 
inhibition or histone deacetylation inhibition, we identified that DNMT3b gene 
expression is subject to histone modifications. Down-regulation of DNMT3b 
resulted in induction of retinoblastoma, p21, and p27, and reduction in cell 
proliferation. These targeted effects were associated with enhanced histone 3 
acetylation and diminished histone methylation.
CONCLUSION: Our findings identify DNMT3b as a putative mediator of epigenetic 
control through histone modifications of gene expression in pituitary cells.