Conserved properties of HP1^Hsα

Heterochromatin protein 1 Hsα (HP1^Hsα) is one of three human proteins that share sequence similarity with Drosophila HP1. HP1 proteins are enriched at centric heterochromatin and play a role in chromatin packaging and gene regulation. In humans, HP1^Hsα is down-regulated in highly invasive/metastatic breast cancer cells, compared to poorly invasive/non-metastatic breast cancer cells. To gain insight into this differential regulation, we have cloned the HP1^Hsα gene and characterized its genomic region. HP1^Hsα is located on human chromosome 12q13.13, 589 bp upstream of the divergently transcribed hnRNPA1 gene. Analysis of the promoter region revealed that differential regulation of HP1^Hsα between the two types of breast cancer cells is lost upon mutation of an USF/c-myc transcription factor binding site located 172 bp upstream of the predicted HP1^Hsα transcription start site. These findings provide insights into the down-regulation of HP1 ^Hsα in highly invasive/metastatic breast cancer cells. To examine the functional properties of HP1^Hsα, experiments were performed using Drosophila melanogaster as a genetic system. When human HP1 ^Hsα was expressed in transgenic Drosophila, silencing of reporter genes inserted at centric and telomeric locations was enhanced. Furthermore, expression of HP1^Hsα rescued the lethality of homozygous Su(var)2-5 mutants lacking HP1. Taken together, these results demonstrate the participation of HP1^Hsα in silent chromatin formation and that HP1^Hsα is a functional homologue of Drosophila HP1.