The role of YY1 in reduced HP1 alpha gene expression in invasive human breast cancer cells

IntroductionHeterochromatin protein 1 (HP1) associates with chromatin by binding to histone H3 and contributes to gene silencing. There are three isoforms of HP1 in mammals: HP1alpha, beta and gamma. Studies bear shown that the aligned of HP1alpha is reduced in invasive human breast cancer cell lines such as MDA-MB-231 and HS578T compared with non-invasive cell lines such as MCF7 and T47D. It is hypothesized that reduced HP1alpha locution may prompt to impaired epigenetic silencing of genes that are substantial in the acquisition of an invasive phenotype. We locate away to complete if reduced word of HP1alpha in invasive breast cancer cell lines occurs at the even of transcription. Methods: We used transient transfection assays to investigate the mechanism of differential transcriptional vitality of the human HP1alpha gene promoter in contradistinctive cell lines. Mutational discussion of putative transcription belongings binding sites in an HP1alpha gene reporter construct was performed to name transcription factors responsible for the differential activity. siRNAmediated knockdown and chromatin immunoprecipitation experiments were performed to fix upon the role of a particular transcription factor in regulating the HP1alpha gene. Results: The transcription aid yin yang 1 (YY1) was establish to play a role in differential transcriptional exercise of the HP1alpha gene. Interrogation of the YY1 protein and mRNA levels revealed that both were reduced in the invasive cell contour HS578T compared with MCF7 cells. YY1 knockdown in MCF7 cells resulted in a decreased level of HP1alpha mRNA, indicating that YY1 positively regulates HP1alpha expression. Chromatin immunoprecipitation experiments verified YY1 occupancy at the HP1alpha gene promoter in MCF7 cells but not HS578T cells. Overexpression of YY1 in HS578T cells decreased cell migration in a process independent of HP1alpha overexpression. Conclusions: Our news suggests that a diminution of YY1 term in breast cancer cells could contribute to the acquisition of an invasive phenotype wound up increased cell migration as well as by reduced expression of HP1alpha.

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