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Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1alpha localization in erythroblasts.

DE GOBBI, Marco;
2011-01-01
2011
Inglese
WOS:000291979800025
21364188
2-s2.0-79959496006
Esperti anonimi
BLOOD
117
6928
6938
10
http://dx.doi.org/10.1182/blood-2010-09-308478
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 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. Cdan1(gt/gt) homozygotes die in utero before the onset of primitive erythropoiesis, suggesting that Cdan1 has other critical roles during embryogenesis.
Anemia; Dyserythropoietic; Congenital; genetics/pathology, Animals, Carrier Proteins; genetics, Cell Line; Tumor, Cells; Cultured, Chromatin; pathology, Chromosomal Proteins; Non-Histone; analysis, Erythroblasts; metabolism/pathology, Female, Glycoproteins; analysis/genetics, Humans, Male, Mice, Mice; Inbred C57BL, Mutation, Vesicular Transport Proteins; analysis
sì
REGNO UNITO DI GRAN BRETAGNA
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262
13
R. Renella;N. A. Roberts;J. M. Brown;M. De Gobbi;L. E. Bird;T. Hassanali;J. A. Sharpe;J. Sloane-Stanley;D. J. P;J. Cordell;V. J. Buckle;D. ...espandi
info:eu-repo/semantics/article
partially_open
03-CONTRIBUTO IN RIVISTA::03A-Articolo su Rivista
03A-Articolo su Rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/89727
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