The three mammalian HP1
proteins, HP1α/CBX5, HP1β/CBX1, and HPγ/CBX3, are involved in
chromatin packing and gene regulation. The HP1α
protein is down-regulated in invasive compared to non-invasive
breast cancer cells and HP1α is a suppressor of cell migration and invasion. In this report, we examined the background for HP1α
protein down-regulation in invasive
breast cancer cells. We identified a strict correlation between HP1α down-regulation at the
protein level and the
mRNA level. The HP1α
mRNA down-regulation in invasive
cancer cells was not caused by
mRNA destabilization.
Chromatin immunoprecipitation analysis of the HP1α gene showed a decrease in the histone mark for transcriptional activity H3-K36 tri-methylation and
RNA polymerase II in invasive
breast cancer cells which correlated with a decreased abundance of basal
transcription factors at the HP1α promoter.
E2F transcription factors regulate HP1α transcription and we identified that E2F5 depletion increased HP1α expression in invasive
breast cancer cells. Finally, we have characterized two HP1α
mRNA isoforms and both HP1α
mRNA isoforms were down-regulated to a similar extend at the transcriptional level in invasive
breast cancer cells. Collectively the presented results show that HP1α down-regulation in invasive
breast cancer cells is primary a transcriptional effect and demonstrates a novel set of mechanisms involved in HP1α transcriptional regulation. The finding that HP1α is down-regulated primarily at the transcriptional level provides a new insight for the further elucidation of the detailed molecular mechanisms causing the HP1α down-regulation in invasive
breast cancer cells.