Saunders W S, Chue C, Goebl M, Craig C, Clark R F, Powers J A, Eissenberg J C, Elgin S C, Rothfield N F, Earnshaw W C
Department of Cell Biology and Anatomy, Johns Hopkins School of Medicine, MD 21205.
J Cell Sci. 1993 Feb;104 ( Pt 2):573-82. doi: 10.1242/jcs.104.2.573.
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 HP1Hs alpha. Epitope mapping experiments using both human and Drosophila HP1 reveal that anti-chromo 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.
我们在硬皮病中鉴定出一种新型自身抗体特异性，我们将其命名为抗染色质抗体。通过免疫印迹法测定，这些抗体识别几种表观分子量在23至25 kDa之间的染色体抗原。抗染色质自身抗体出现在10%至15%的抗着丝粒抗体（ACA）患者血清中。我们使用抗染色质抗体筛选人类表达文库，获得了编码一种25 kDa染色体自身抗原的cDNA克隆。DNA序列分析表明，该蛋白质是果蝇异染色质蛋白HP1的人类同源物。我们将克隆的蛋白质命名为HP1Hsα。使用人类和果蝇HP1进行的表位作图实验表明，抗染色质抗体靶向该蛋白质氨基末端的一个区域。该区域包含一个保守基序，即染色质结构域（或HP1/Pc盒），最初是通过将果蝇HP1与多梳基因产物进行比较而识别出来的。这两种蛋白质都被认为在形成抑制基因表达的染色质结构中发挥作用。因此，抗染色质抗体定义了一种新型自身抗体，它识别在多种染色体蛋白质上发现的保守结构基序。
