The interplay between Heterochromatin- Protein 1 (HP1) and H2A.Z in cancer progression — ASN Events

The interplay between Heterochromatin- Protein 1 (HP1) and H2A.Z in cancer progression (#274)

Bhumika Azad 1 , Renae Domaschenz 1 , David Tremethick 1
  1. John Curtin School of Medical Research, ANU, Acton, ACT, Australia

Eukaryotic gene regulation is associated with the structural organization of the genome. The basis for this structural organization is chromatin. Any disruption in chromatin structure causes alteration of essential regulatory genes which is directly associated with cancer initiation and progression.

Determining how chromatin is remodelled is essential to understand how epigenetic states are altered in cancer. One of the important regulators of chromatin packaging and genomic stability is the architectural chromatin binding protein, heterochromatin protein 1 (HP1). Any disruption of HP1 expression can alter the chromatin status of multiple genomic regions, simultaneously affecting the expression of hundreds of down-stream target genes. Another important regulator of chromatin function is the histone variant, H2A.Z. A number of microarray studies have shown high levels of H2A.Z expression in cancer. Data from our lab has shown that H2A.Z co-localizes with HP1α at discrete foci to enhance chromatin compaction. These observations lead us to hypothesis that the relationship between HP1α and H2A.Z may be important for maintaining heterochromatin integrity.

To gain insights into the role of HP1 isoforms HP1α and HP1β expression in the progression of breast cancer, we developed HP1α, HP1β and H2A.Z single and HP1α/β; HP1α/H2A.Z double shRNA knockdown breast epithelial cell lines. Here we show characterization of the cell cycle, cell proliferation, and nuclear and chromosomal location changes in response to various knockdown combinations. Uncovering the interplay between HP1 isoforms and H2A.Z will further our understanding of the role they each play in genome instability leading to cancer progression.

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