Heterochromatin protein HP1 Hsβ (p25β) and its localization with centromeres in mitosis

Abstract

Some autoimmune sera containing anticentromere autoantibodies also recognize a doublet of Mr 23 000 (p23) and 25 000 (p25) in addition to CENP (centromere protein)-A (Mr 19 000), -B (Mr 80 000), and -C (Mr 140 000). A p25 antigen (HP1(Hsalpha)) has been shown to be a human homolog of Drosophila HP1 (heterochromatin protein 1). We have isolated a cDNA clone encoding another form of p25 (HP1(Hsbeta ) or p25beta) from a lambdaZap HepG2 library using human autoimmune serum. The deduced amino acid sequence of the clone contained a conserved chromodomain (chromatin modifier domain) in the N-terminal region and a heterochromatin binding domain in the C-terminal region. In immunofluorescence experiments, only affinity purified antibodies reactive with the C-terminal (amino acids 70-185) domain showed nucleoplasmic and heterochromatin staining, whereas N-terminal (amino acids 1-115) specific antibodies were nonreactive. In metaphase chromosome spreads, the C-terminal domain antibody was also localized to the centromeric regions of chromosomes. Association with centromeres was most prominent at anaphase and changed to a more generalized association with whole chromosomes in telophase. The cooccurrence of autoantibodies to centromere proteins and HP1 in certain autoimmune diseases might be a reflection of coordinated immune responses to these closely associated sets of proteins.

Highly parallel identification of essential genes in cancer cells

“…1D). The 5 genes include 3 with well-established roles in FASinduced apoptosis (11,(13)(14)(15) (FAS, FADD, and CASP8) and 2 previously undescribed genes-ARID1A, a SWI/SNF chromatin remodeling complex component (16,17), and CBX1, a chromatin silencing protein (18). For all 5 genes, the effective shRNAs also inhibited both FAS-induced CASPASE 8 cleavage and FASinduced mitochondrial leakage (Fig.…”

Dynamic Regulation of Effector Protein Binding to Histone Modifications: The Biology of HP1 Switching

“…Different studies using different cell lines and experimental approaches have shown partial to complete loss of HP1 from mitotic chromatin. [43][44][45][46][47][48] The consensus seems that at this stage of the cell cycle, all of HP1b and HP1g, as well as the majority of HP1a, dissociate from chromatin. Only a fraction of HP1a remains localized at the centromeres.…”

“…46 If phosphorylation of H3S10 is indeed sufficient to abolish interaction of the chromo domain of all HP1 isoforms with H3K9me3, globally releasing them from mitotic chromatin, then separate mechanisms must exist to anchor HP1a at the centromere. Interestingly, HP1a itself is subject to extensive post-translational modifications, 44 which appear to regulate its association with other chromatin components. 61 In vitro, the CPC complex phosphorylates residues in the HP1a hinge region (our unpublished observations), which might mediate the retention of this isoform at the centromere, possibly via interaction with the CPC and/or phosphorylated histone H3.…”

Localisation of histone macroH2A1.2 to the XY-body is not a response to the presence of asynapsed chromosome axes

“…HP1β has therefore been implicated in a wide range of possible functions including transcriptional repression (Ryan et al, 1999), transgene silencing (Festenstein et al, 1999), chromosome segregation (Wang et al, 2000) and nuclear envelope reassembly (Kourmouli et al, 2000). HP1β is predominantly found in pericentromeric constitutive heterochromatin in mitotic (Wregett et al, 1994;Furuta et al, 1997) and meiotic cells (Motzkus et al, 1999) and it is concentrated in the XY-body of late-pachytene and diplotene spermatocytes (Motzkus et al, 1999;Turner et al, 2001). HP1β is a dose-dependent modifier of a variegating position effect (Festenstein et al, 1999).…”