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

William S. Saunders, Calvin Chue, Mark Goebl, Carolyn Craig, Robert F. Clark, James A. Powers, Joel C. Eissenberg, Sarah C R Elgin, Naomi F. Rothfield, William C. Earnshaw

Research output: Contribution to journalArticle

144 Citations (Scopus)

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
Pages (from-to)573-582
Number of pages10
JournalJournal of Cell Science
Volume104
Issue number2
StatePublished - Feb 1993

Fingerprint

Heterochromatin
Centromere
Molecular Cloning
Autoantibodies
Proteins
Drosophila
Anti-Idiotypic Antibodies
Epitope Mapping
Drosophila Proteins
Antibodies
Autoantigens
Gene Library
DNA Sequence Analysis
Chromatin
Clone Cells
Drosophila heterochromatin protein 1
Gene Expression
Antigens
Serum
Genes

Keywords

  • Autoantibodies
  • Chromatin
  • Heterochromatin
  • HP1

ASJC Scopus subject areas

  • Cell Biology

Cite this

Molecular cloning of a human homologue of Drosophila heterochromatin protein HP1 using anti-centromere autoantibodies with anti-chromo specificity. / Saunders, William S.; Chue, Calvin; Goebl, Mark; Craig, Carolyn; Clark, Robert F.; Powers, James A.; Eissenberg, Joel C.; Elgin, Sarah C R; Rothfield, Naomi F.; Earnshaw, William C.

In: Journal of Cell Science, Vol. 104, No. 2, 02.1993, p. 573-582.

Research output: Contribution to journalArticle

Saunders, WS, Chue, C, Goebl, M, Craig, C, Clark, RF, Powers, JA, Eissenberg, JC, Elgin, SCR, Rothfield, NF & Earnshaw, WC 1993, 'Molecular cloning of a human homologue of Drosophila heterochromatin protein HP1 using anti-centromere autoantibodies with anti-chromo specificity', Journal of Cell Science, vol. 104, no. 2, pp. 573-582.
Saunders, William S. ; Chue, Calvin ; Goebl, Mark ; Craig, Carolyn ; Clark, Robert F. ; Powers, James A. ; Eissenberg, Joel C. ; Elgin, Sarah C R ; Rothfield, Naomi F. ; Earnshaw, William C. / Molecular cloning of a human homologue of Drosophila heterochromatin protein HP1 using anti-centromere autoantibodies with anti-chromo specificity. In: Journal of Cell Science. 1993 ; Vol. 104, No. 2. pp. 573-582.
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