Transcriptional regulation of POSTN gene expression by YY1 and BRCA1

Periostin (POSTN), an osteoblast-specific secreted protein involved in cell adhesion activity for bone formation and development by the epithelial cell-derived tumors, leads to a significant enhancement in angiogenesis and tumorigenesis. Despite the complex correlation of dysregulated periostin expression levels both in physiological and neoplastic conditions, very little is known about the mechanisms underlying its transcriptional control. Here, we report the initial characterization of the human POSTN gene promoter and show that its activity in HeLa cells depends on the binding of YingYang-1 (YY1) zinc finger transcription factor. We mapped, by ChIP and EMSA analysis, the functional YY1-binding site on human POSTN gene promoter at position -604. In order to define the functional role of YY1 binding on the expression of the human periostin gene, we performed RNA interference experiments to knock down endogenous YY1 and analyzed the effects on periostin mRNA levels. We found, by RT-PCR experiments, a consistent and reproducible increase of POSTN transcript in the HeLa cells silenced for YY1. Conversely, over-expression of YY1 results in a significant down regulation of POSTN gene when compared to control HeLa cells. Next, ChIP and sequential ChIP showed that the repression observed on POSTN gene expression is not solely ascribable to the YY1 activity. In fact, immunoprecipitation experiments revealed that YY1 interact with BRCA1 to form a complex that co-ordinately represses POSTN expression via the functional YY1-binding site. These findings shed light in the transcriptional control of the POSTN gene expression and provide evidences supporting the potential role of this protein in BRCA1-dependent tumorigenesis. Abstracts P11 – Cancer biology