Does heterochromatin protein 1 always follow code?

Abstract

Heterochromatin protein 1 (HP1) is a conserved chromosomal protein that participates in chromatin packaging and gene silencing. A loss of HP1 leads to lethality in Drosophila and correlates with metastasis in human breast cancer cells. On Drosophila polytene chromosomes HP1 is localized to centric regions, telomeric regions, in a banded pattern along the fourth chromosome, and at many sites scattered throughout the euchromatic arms. Recently, one mechanism of HP1 chromosome association was revealed; the amino-terminal chromo domain of HP1 interacts with methylated lysine nine of histone H3, consistent with the histone code hypothesis. Compelling data support this mechanism of HP1 association at centric regions. Is this the only mechanism by which HP1 associates with chromosomes? Interest is now shifting toward the role of HP1 within euchromatic domains. Accumulating evidence in Drosophila and mammals suggests that HP1 associates with chromosomes through interactions with nonhistone chromosomal proteins at locations other than centric heterochromatin. Does HP1 play a similar role in chromatin packaging and gene regulation at these sites as it does in centric heterochromatin? Does HP1 associate with the same proteins at these sites as it does in centric heterochromatin? A first step toward answering these questions is the identification of sequences associated with HP1 within euchromatic domains. Such sequences are likely to include HP1 ''target genes'' whose discovery will aid in our understanding of HP1 lethality in Drosophila and metastasis of breast cancer cells.

Breast Cancer Metastasis Suppressor 1 (BRMS1) Forms Complexes with Retinoblastoma-binding Protein 1 (RBP1) and the mSin3 Histone Deacetylase Complex and Represses Transcription

“…MTA1 has subsequently been shown to repress estrogen receptor-dependent transcription in an HDAC-dependent manner (48). Likewise, loss of expression of heterochromatin protein 1 (HP1) has been associated with acquisition of metastatic potential in human breast cancer (49). Together, these findings support the hypothesis that regulation of the transcriptome by a variety of mechanisms is a critical determinant of cancer spread.…”

Epigenetics and cancer

“…Whereas the three mammalian HP1 members all hold chromodomains capable of recognizing the methylated Lys 9 on histone H3 Lachner et al 2001), the differences in subnuclear localizations point to the presence of additional mechanisms for localizing and tethering HP1 proteins. HP1 has been found to interact with many different proteins, spanning from histones over transcriptional regulators to proteins involved in DNA replication and nuclear architecture (for review, see Li et al 2002). Loss of Suv39h in mice results in the displacement of HP1 proteins from pericentromeric heterochromatin, resulting in anaploidy and cancer (Peters et al 2001).…”

Heterochromatin?many flavours, common themes

“…It is associated with many forms of heterochromatin including centromeres, telomeres, silent gene promoters and triplet repeat expansions, with the mammalian Xi being a notable exception. (34)(35)(36) The interaction central to heterochromatin formation and maintenance is the three-way interaction between HP1 or Polycomb, methylated lysine residues and HMTs (37) (Fig. 4A).…”

“…(64) Macro H2A also interacts with HP1 (35) and may bind RNA. (65) The histone variant H2A.Z is involved in the establishment of budding yeast silent mating type loci, where it is also responsible for restricting the spread of silent chromatin.…”

“…(97) The peripheral localisation of these clusters may be due at least in part to the interaction of HP1 with nuclear lamins. (35) Some but not all genes utilise these clusters of inactive chromatin as an additional layer of transcriptional control. (96,(98)(99)(100) Silenced imprinted alleles are also located towards the exterior of a nucleus.…”