Molecular cloning of a human homologue of Drosophila heterochromatin protein HP1 using anti-centromere autoantibodies with anti-chromo specificity

W. S. Saunders, C. Chue, M. Goebl, C. Craig, R. F. Clark, J. A. Powers, J. C. Eissenberg, S. C.R. Elgin, N. F. Rothfield, W. C. Earnshaw

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Abstract

We have identified a novel autoantibody specificity in scleroderma that we term anti-chromo. These antibodies recognize several chromosomal antigens with apparent molecular mass of between 23 and 25 kDa, as determined by immunoblots. Anti-chromo autoantibodies occur in 10-15% of sera from patients with anti-centromere antibodies (ACA). We used anti-chromo antibodies to screen a human expression library and obtained cDNA clones encoding a 25 kDa chromosomal autoantigen. DNA sequence analysis reveals this protein to be a human homologue of HP1, a heterochromatin protein of Drosophila melanogaster. We designate our cloned protein HP1Hsα. Epitope mapping experiments using both human and Drosophila HP1 reveal that antichromo antibodies target a region at the amino, terminus of the protein. This region contains a conserved motif, the chromo domain (or HP1/Pc box), first recognized by comparison of Drosophila HP1 with the Polycomb gene product. Both proteins are thought to play a role in creating chromatin structures in which gene expression is suppressed. Anti-chromo thus defines a novel type of autoantibody that recognizes a conserved structural motif found on a number of chromosomal proteins.

Original languageEnglish (US)
Pages (from-to)573-582
Number of pages10
JournalJournal of cell science
Volume104
Issue number2
StatePublished - Jan 1 1993

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Keywords

  • Autoantibodies
  • Chromatin
  • Heterochromatin
  • HP1

ASJC Scopus subject areas

  • Cell Biology

Cite this

Saunders, W. S., Chue, C., Goebl, M., Craig, C., Clark, R. F., Powers, J. A., Eissenberg, J. C., Elgin, S. C. R., Rothfield, N. F., & Earnshaw, W. C. (1993). Molecular cloning of a human homologue of Drosophila heterochromatin protein HP1 using anti-centromere autoantibodies with anti-chromo specificity. Journal of cell science, 104(2), 573-582.