Disease relevance of Cbx5

• In order to investigate the role of the murine HP1-like protein M31 in heterochromatin formation and gene silencing, recombinant CSD was overexpressed in Escherichia coli and crystallized using the hanging-drop vapour-diffusion method with PEG 4000 as precipitant [1].
• We have recently purified and partially sequenced a new T cell-derived lymphokine with growth factor activity for B cell hybridomas and plasmacytomas, which we named interleukin HP1 (HP1) [2].
• Antimicrobial susceptibility of the Lyme disease Borrelia, strain HP1 vi, isolated from the tick ixodes persulcatus in Hokkaido, Japan, was determined in vitro and in vivo [3].

High impact information on Cbx5

• The chromodomain of mouse HP1 (and Swi6 in S. pombe) binds H3 methylated at Lys9, and methylation at this site is thought to mark and promote heterochromatin assembly [4].
• Unexpectedly, Ikaros localized to discrete heterochromatin-containing foci in interphase nuclei, which comprise clusters of centromeric DNA as defined by gamma-satellite sequences and the abundance of heterochromatin protein-1 (HP-1) [5].
• Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9 [6].
• Methylation of lysine 9 in histone H3 is recognized by heterochromatin protein 1 (HP1), which directs the binding of other proteins to control chromatin structure and gene expression [6].
• In vivo, heterochromatin association of HP1 proteins is lost in Suv39h double-null primary mouse fibroblasts but is restored after the re-introduction of a catalytically active SWUV39H1 HMTase [7].

Biological context of Cbx5

• The heterochromatin protein 1 (HP1) family of proteins is involved in gene silencing via the formation of heterochromatic structures [8].
• A His(6)-tagged peptide representing this region inhibited recruitment of LAP2beta and B-type lamins around the surfaces of condensed chromosomes, suggesting involvement of HP1 proteins in nuclear envelope reassembly [9].
• Methylation of histone H3 at lysine 9 (H3-K9) mediates heterochromatin formation by forming a binding site for HP1 and also participates in silencing gene expression at euchromatic sites [10].
• Collectively, these data provide compelling evidence for a dynamic nuclear compartmentalization of TIF1beta that is regulated during cell differentiation through a mechanism that requires HP1 interaction [11].
• Recent genetic and biochemical studies link H3-lysine 9 (H3-K9) methylation to HP1-mediated heterochromatin formation and gene silencing [12].

Anatomical context of Cbx5

• In line with these observations, recombinant HP1 proteins exhibited saturable binding to purified nuclear envelopes and stained the nuclei of detergent-permeabilized cells in a rim-like fashion [9].
• TIF1delta, a novel HP1-interacting member of the transcriptional intermediary factor 1 (TIF1) family expressed by elongating spermatids [13].
• Future investigations should follow changes in epigenetic markers and levels of HP1 proteins during granulopoiesis and bacterial activation of neutrophils [14].
• These granulocytes revealed negligible amounts of HP1 alpha and beta, but exhibited detectable levels of HP1 gamma [14].
• The outgrowing SUV39H1-immortalized erythroblasts can maintain a diploid karyotype despite deregulation of several tumour suppressor proteins and dispersed distribution of the heterochromatin component HP1 [15].

Associations of Cbx5 with chemical compounds

• Most HP1 typically dissociates from chromosomes during mitosis, but if phosphorylation of H3 serine 10 is inhibited, HP1 remains chromosome-bound throughout mitosis [16].
• H3 phosphorylation by Aurora B is therefore part of a 'methyl/phos switch' mechanism that displaces HP1 and perhaps other proteins from mitotic heterochromatin [16].
• Here we show that, in response to viral infection or after treatment with poly(rI).poly(rC), L cells produce a factor that is capable of supporting the in vitro growth and survival of HP1-dependent cell lines [2].
• By contrast, in conjunction with interleukin 1, HP1 became a major growth and differentiation factor not only for B cells activated with anti-immunoglobulin antibodies but also for dextran sulfate-stimulated and even for unstimulated B cells [17].
• Strain HP1 vi was most susceptible to minocycline (MBC, 0.2 micrograms/ml) [3].

Physical interactions of Cbx5

• KAP-1 directly interacts with heterochromatin protein 1 (HP1), a dose-dependent regulator of heterochromatin-mediated silencing [18].
• HP1 binds specifically to Lys26-methylated histone H1.4, whereas simultaneous Ser27 phosphorylation blocks HP1 binding [19].

Co-localisations of Cbx5

• Unlike DNMT1, which localizes to replication foci during S-phase in murine embryonic fibroblasts, Dnmt3a co-localizes with heterochromatin protein 1 alpha (HP1 alpha) and methyl-CpG binding proteins throughout the cell cycle to late-replicating pericentromeric heterochromatin [20].

Other interactions of Cbx5

• The HP1 class of chromobox (Cbx) genes encode an evolutionarily conserved family of proteins involved in the packaging of chromosomal domains into a repressive heterochromatic state [21].
• Mice possess two structural homologues of Drosophila HP1, termed M31 and M32 (Singh et al., 1991) [22].
• This change is also associated with global relocation of heterochromatin protein HP1 and histone H3 methyltransferase Suv39h1 away from constitutive heterochromatin; however, it does not affect DNA methylation or chromosome segregation, phenotypes commonly associated with impaired histone H3(K9) methylation [23].
• Contiguous arrangement of p45 NFE2, HnRNP A1, and HP1 alpha on mouse chromosome 15 and human chromosome 12: evidence for suppression of these genes due to retroviral integration within the Fli-2 locus [24].

Analytical, diagnostic and therapeutic context of Cbx5

• RESULTS: Immunostaining and immunoblotting procedures were employed to study the presence of repressive histone modifications and HP1 proteins in normal human and mouse blood neutrophils, and in vitro differentiated granulocytes of the mouse promyelocytic (MPRO) system [14].
• To decrease gene silencing, the chromo domain (CD) in the M31 (the main HP1 in mouse) was deleted by site-directed mutagenesis [25].
• It could be traced to a single component, which behaved like HP1 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and reverse phase high performance liquid chromatography, and was completely inhibited by a rabbit anti-HP1 antiserum [26].

References