Heterochromatin protein HP1Hsbeta (p25beta) and its localization with centromeres in mitosis.
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.
Furuta
K
K
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Chan
E K
EK
Kiyosawa
K
K
Reimer
G
G
Luderschmidt
C
C
Tan
E M
EM
D016475:3T3 Cells / Q000276:immunology; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies; D001483:Base Sequence; D002503:Centromere / Q000235:genetics*; D002843:Chromatin / Q000235:genetics; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000276:immunology; D002874:Chromosome Mapping; D003001:Cloning, Molecular / Q000379:methods; D003429:Cross Reactions; D004330:Drosophila / Q000235:genetics; D005260:Female; D006801:Humans; D007106:Immune Sera; D051379:Mice; D008938:Mitosis; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D017422:Sequence Analysis, DNA
D001323:Autoantibodies; C000715594:CBX5 protein, human; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D007106:Immune Sera; D000090266:Chromobox Protein Homolog 5