Abstract
The stability of pericentromeric heterochromatin is maintained by repressive epigenetic control mechanisms, and failure to maintain this stability may cause severe diseases such as immune deficiency and cancer. Thus, deeper insight into the epigenetic regulation and deregulation of pericentromeric heterochromatin is of high priority. We and others have recently demonstrated that pericentromeric heterochromatin domains are often epigenetically reprogrammed by Polycomb proteins in premalignant and malignant cells to form large subnuclear structures known as Polycomb bodies. This may affect the regulation and stability of pericentromeric heterochromatin domains and/or the distribution of Polycomb factors to support tumorigeneses. Importantly, Polycomb bodies in cancer cells may be targeted by the cancer/testis-related SSX proteins to cause derepression and genomic instability of pericentromeric heterochromatin. This review will discuss the interplay between SSX and Polycomb factors in the repression and stability of pericentromeric heterochromatin and its possible implications for tumor biology.
Highlights
The stability of pericentromeric heterochromatin is maintained by repressive epigenetic control mechanisms, and failure to maintain this stability may cause severe diseases such as immune deficiency and cancer
The PcG family comprises a diverse set of proteins that assemble into transcriptional-repressive complexes, called PcG repressive complexes (PRCs), that epigenetically modify chromatin
PRC2 comprises the methyltransferase enhancer of zeste homologue 2 (EZH2), the enzymatic activity of which depends on the binding of two other core subunits, embryonic ectoderm development (EED) and suppressor or zeste
Summary
Polycomb-group (PcG) proteins have been the subject of great scientific interest since it was discovered that they repressed the expression of Drosophila HOX genes and played a role in normal. Two other PRC2 have been identified; PRC2.1 with Tudor-domain containing PCL1/2/3 proteins, and PRC2.2 containing the accessory zinc-finger proteins AEBP2 and JARID2 [2,9,10,12]. Both types of PRC complexes are able to modify histones, the tri-methylation of lysine. The combinatorial assembly of mammalian PRC1 subunit homologues gives rise to various functionally distinct ncPRC1 complexes that can occur and function independent of PRC2 and can recruit PRC2 [11,15,16,17], suggesting that PcG recruitment to chromatin and gene silencing is more complicated and complex than first assumed
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