The role of YY1 in reduced HP1 alpha gene expression in invasive human breast cancer cells
Lieberthal JG et al. - In a study to determine whether reduced expression of heterochromatin protein 1 (HP1)-α in invasive breast cancer cell lines occurs at the level of transcription, these data suggest that a reduction of YY1 expression in breast cancer cells could contribute to acquisition of an invasive phenotype through increased cell migration as well as by reduced expression of HP1-α. Methods- Transient transfection assays were used to investigate the mechanism of differential transcriptional activity of the human HP1-α gene promoter in different cell lines.
- Mutational analysis of putative transcription factor binding sites in an HP1-α gene reporter construct was performed to identify transcription factors responsible for the differential activity.
- siRNA-mediated knockdown and chromatin immunoprecipitation experiments were performed to determine the role of a specific transcription factor in regulating the HP1-α gene.
Results- Transcription factor yin yang 1 (YY1) was found to play a role in differential transcriptional activity of the HP1-α gene.
- Examination of the YY1 protein and mRNA levels revealed that both were reduced in the invasive cell line HS578T vs MCF7 cells.
- YY1 knockdown in MCF7 cells resulted in a decreased level of HP1-α mRNA, indicating that YY1 positively regulates HP1-α expression.
- Chromatin immunoprecipitation experiments verified YY1 occupancy at the HP1-α gene promoter in MCF7 cells, but not HS578T cells.
- Overexpression of YY1 in HS578T cells decreased cell migration in a manner independent of HP1-α overexpression.
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