Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1 alpha localization in erythroblasts
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 demonstrat...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2011
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| _version_ | 1797086551573790720 |
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| author | Renella, R Roberts, N Brown, J De Gobbi, M Bird, L Hassanali, T Sharpe, J Sloane-Stanley, J Ferguson, D Cordell, J Buckle, V Higgs, D Wood, W |
| author_facet | Renella, R Roberts, N Brown, J De Gobbi, M Bird, L Hassanali, T Sharpe, J Sloane-Stanley, J Ferguson, D Cordell, J Buckle, V Higgs, D Wood, W |
| author_sort | Renella, R |
| collection | OXFORD |
| description | 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 byWestern blot.Adetailed analysis of chromatin structure in CDA-1 erythroblasts shows no abnormalities in overall histone composition, and the genomewide epigenetic landscape of several histone modifications is maintained. However, immunofluorescence analysis of intermediate erythroblasts from patients with CDA-1 reveals abnormal accumulation of HP1α in the Golgi apparatus. A link between mutant codanin-1 and the aberrant localization of HP1α is supported by the finding that codanin-1 can be coimmunoprecipitated by anti-HP1α 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. Cdan1gt/gt homozygotes die in utero before the onset of primitive erythropoiesis, suggesting that Cdan1 has other critical roles during embryogenesis. © 2011 by The American Society of Hematology. |
| first_indexed | 2024-03-07T02:23:43Z |
| format | Journal article |
| id | oxford-uuid:a4dbfb43-e843-46fa-b856-a4e6499352ff |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:23:43Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:a4dbfb43-e843-46fa-b856-a4e6499352ff2022-03-27T02:36:31ZCodanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1 alpha localization in erythroblastsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a4dbfb43-e843-46fa-b856-a4e6499352ffEnglishSymplectic Elements at Oxford2011Renella, RRoberts, NBrown, JDe Gobbi, MBird, LHassanali, TSharpe, JSloane-Stanley, JFerguson, DCordell, JBuckle, VHiggs, DWood, WCongenital 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 byWestern blot.Adetailed analysis of chromatin structure in CDA-1 erythroblasts shows no abnormalities in overall histone composition, and the genomewide epigenetic landscape of several histone modifications is maintained. However, immunofluorescence analysis of intermediate erythroblasts from patients with CDA-1 reveals abnormal accumulation of HP1α in the Golgi apparatus. A link between mutant codanin-1 and the aberrant localization of HP1α is supported by the finding that codanin-1 can be coimmunoprecipitated by anti-HP1α 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. Cdan1gt/gt homozygotes die in utero before the onset of primitive erythropoiesis, suggesting that Cdan1 has other critical roles during embryogenesis. © 2011 by The American Society of Hematology. |
| spellingShingle | Renella, R Roberts, N Brown, J De Gobbi, M Bird, L Hassanali, T Sharpe, J Sloane-Stanley, J Ferguson, D Cordell, J Buckle, V Higgs, D Wood, W Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1 alpha localization in erythroblasts |
| title | Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1 alpha localization in erythroblasts |
| title_full | Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1 alpha localization in erythroblasts |
| title_fullStr | Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1 alpha localization in erythroblasts |
| title_full_unstemmed | Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1 alpha localization in erythroblasts |
| title_short | Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1 alpha localization in erythroblasts |
| title_sort | codanin 1 mutations in congenital dyserythropoietic anemia type 1 affect hp1 alpha localization in erythroblasts |
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