| First Author | Renella R | Year | 2011 |
| Journal | Blood | Volume | 117 |
| Issue | 25 | Pages | 6928-38 |
| PubMed ID | 21364188 | Mgi Jnum | J:174639 |
| Mgi Id | MGI:5140270 | Doi | 10.1182/blood-2010-09-308478 |
| Citation | Renella R, et al. (2011) Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1{alpha} localization in erythroblasts. Blood 117(25):6928-38 |
| abstractText | Congenital dyserythropoietic anemia type 1 (CDA-1), a rare inborn anemia characterized by abnormal chromatin ultrastructure in erythroblasts, is caused by abnormalities in codanin-1, a highly conserved protein of unknown function. We have produced 3 monoclonal antibodies to codanin-1 that demonstrate its distribution in both nucleus and cytoplasm by immunofluorescence and allow quantitative measurements of patient and normal material by Western blot. A detailed analysis of chromatin structure in CDA-1 erythroblasts shows no abnormalities in overall histone composition, and the genome-wide epigenetic landscape of several histone modifications is maintained. However, immunofluorescence analysis of intermediate erythroblasts from patients with CDA-1 reveals abnormal accumulation of HP1alpha in the Golgi apparatus. A link between mutant codanin-1 and the aberrant localization of HP1alpha is supported by the finding that codanin-1 can be coimmunoprecipitated by anti-HP1alpha antibodies. Furthermore, we show colocalization of codanin-1 with Sec23B, the protein defective in CDA-2 suggesting that the CDAs might be linked at the molecular level. Mice containing a gene-trapped Cdan1 locus demonstrate its widespread expression during development. Cdan1(gt/gt) homozygotes die in utero before the onset of primitive erythropoiesis, suggesting that Cdan1 has other critical roles during embryogenesis. |
