Codanin-1, the protein encoded by the gene mutated in congenital dyserythropoietic anemia type I (CDAN1), is cell cycle-regulated

Noy-Lotan, Sharon; Dgany, Orly; Lahmi, Roxane; Marcoux, Nathaly; Krasnov, Tanya; Yissachar, Nissan; Ginsberg, Doron; Motro, Benny; Resnitzky, P; Yaniv, Isaac; Kupfer, Gary M.; Tamary, Hannah

doi:10.3324/haematol.2008.003327

Cited by 32 publications

(29 citation statements)

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“…28 Differences with the data presented by Noy-Lotan et al 28 may have resulted from their use of a polyclonal rabbit antibody, whose specificity was not as clearly defined as for our series of murine monoclonal antibodies. Furthermore, these investigators' experiments were performed in nonerythroid cell lines, rather than in primary erythroid cells as studied here.…”

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confidence: 58%

Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1α localization in erythroblasts

Renella

Roberts

Brown

et al. 2011

Blood

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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 genomewide epigenetic landscape of several histone modifications is maintained. However, immunofluorescence analysis of intermediate erythroblasts from patients with CDA-1 reveals abnormal accumulation of HP1␣ in the Golgi apparatus. A link between mutant codanin-1 and the aberrant localization of HP1␣ is supported by the finding that codanin-1 can be coimmunoprecipitated by anti-HP1␣ 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. (Blood. 2011;117(25): 6928-6938) IntroductionThe congenital dyserythropoietic anemias (CDAs) are a heterogeneous group of rare inborn disorders mainly affecting erythropoiesis. 1 Distinct from other inherited bone marrow failure syndromes, they are marked by morphologic abnormalities of the erythroblasts that lead to ineffective erythropoiesis/dyserythropoiesis, whereas the other hematopoietic lineages appear to be unaffected. Based largely on the dysplastic changes observed in erythroblasts by light and electron microscopy, the CDAs have been divided into 3 major types, designated CDA types 1, 2, and 3 2 ; causative genes have been identified for CDA-1 (CDAN1/codanin-1) 3 and CDA-2 (CDAN2/Sec23B), 4 whereas only the chromosomal locus is known for . 5 In CDA-1, the majority of cases come to attention during childhood and adolescence, often within episodes of erythropoietic stress (ie, infection, and in young women, pregnancy). 6,7 Severe presentations can include gallstones, chronic hyperbilirubinemia, and/or extramedullary hematopoietic foci in the parietal and frontal bones of the skull (as observed in thalassemia). Although iron overloading is rarely the revelatory sign, it seems to be present in the majority of patients after childhood. In some cases, skeletal or other dysmorphic features can be identified, including short stature, distal limb and nail malformations, vertebral deformations/dysplasias, and skin pigmentation defects. 1 The anemia is macrocytic with mean corpuscular volumes up to 120 fL, and the blood smear shows anisopoikilocytosis, basophilic stippling, and an inadequate reticulocyte response compared with hemolytic anemias....

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Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1α localization in erythroblasts

Renella

Roberts

Brown

et al. 2011

Blood

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“…No patients have been found to be homozygous for a null-type mutation, suggesting that the complete absence of functional codanin-1 may be lethal [31,32]. Recently, codanin-1 was found to be localized to the heterochromatin in interphase cells and was transcriptionally regulated by E2F1, a member of a transcription factor family involved in cell cycling [33].…”

Section: Cda Type Imentioning

confidence: 98%

Congenital dyserythropoietic anemia

Kamiya

Manabe

2010

Int J Hematol

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Congenital dyserythropoietic anemias (CDAs) are a heterogeneous group of rare hereditary disorders of erythropoiesis characterized by morphologic abnormal erythroblasts in the bone marrow. Three types of the disease are known as type I, II and III, and the variant type of CDA and several minor subgroups of CDA have been also reported since the first classification. Recently, responsible genes for type I (CDAN1) and type II (SEC23B) have been identified and the molecular pathogenesis of the disease is currently being explored. Although CDAs rarely transform to myelodysplastic syndrome or leukemia, the disease is important to understand the mechanism of hemopoiesis in humans.

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“…In 2009, Tamary et al showed that codanin-1 is a direct transcriptional target of the E2F1 transcription factor and that its levels increase during S-phase and decrease during mitosis. 55 In another study, Tamary and colleagues found that codanin-1 binds to Asf1a (histone H3/H4 chaperone anti-silencing 1), 56 involved in the chromatin structure dynamics by its role in nucleosome assembly and disassembly. In particular, Asf1a binds histone H3/H4 in the cytoplasm and in complex with importin-4 accompanies histone dimers into the nucleus where they are transferred to downstream chromatin assembly factors.…”

Section: Cda Type Imentioning

confidence: 99%

Clinical aspects and pathogenesis of congenital dyserythropoietic anemias: from morphology to molecular approach

2012

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Congenital dyserythropoietic anemias belong to a group of inherited conditions characterized by a maturation arrest during erythropoiesis with a reduced reticulocyte production in contrast with erythroid hyperplasia in bone marrow. The latter shows specific morphological abnormalities that allowed for a morphological classification of these conditions mainly represented by congenital dyserythropoietic anemias types I and II. The identification of their causative genes provided evidence that these conditions have different molecular mechanisms that induce abnormal cell maturation and division. Some altered proteins seem to be involved in the chromatin assembly, such as codanin-1 in congenital dyserythropoietic anemia I. The gene involved in congenital dyserythropoietic anemia II, the most frequent form, is SEC23B. This condition seems to belong to a group of diseases attributable to defects in the transport of newly synthesized proteins from endoplasmic reticulum to the Golgi. This review will analyze recent insights in congenital dyserythropoietic anemias types I and II. It will also attempt to clarify the relationship between mutations in causative genes and the clinical phenotype of these conditions. Key words: dyserythropoiesis, congenital dyserythropoietic anemia, red blood cells, inherited anemias.Citation: Iolascon A, Esposito MR, and Russo R. Clinical aspects and pathogenesis of congenital dyserythropoietic anemias: from morphology to molecular approach. Haematologica 2012;97(12): 1786-1794. doi:10.3324/haematol.2012 This is an open-access paper. ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o nto distinguish without molecular evaluation. 7,8 Recent identification of several causative genes could help reclassify these disorders (Table 1). Variant forms are very rare and this, up to now, has compromised further molecular studies. Linkage studies had previously been the main tool to clarify the genetics of Mendelian disorders; however, extremely rare disorders or sporadic cases caused by de novo variants are not appropriate for this type of study design. Exome sequencing is now becoming technically feasible and more cost-effective due to the recent advances in high-throughput sequence capture methods and next-generation sequencing technologies that have offered new opportunities for research into Mendelian disorders. 9 We suggest that the use of these new technologies will lead to the identification of new causative genes in CDA variants in the near future. In particular, this review will deal with new insights on the two most frequent forms of CDAs: types I and II. Epidemiology of CDAsUntil December 2011, 712 cases from 614 families were included in the German CDA Registry, 10,11 whereas 206Clinical aspects and pathogenesis of CDAs haematologica | 2012; 97 (12) 1787 © F e r r a t a S t o r t i F o u n d a t i o ncases from 183 families were enrolled in the Italian CDA registry (A Iolascon, unpublished data, 2011 Although CDA II patients are to be found right across the Italian peninsula, the maj...

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Codanin-1, the protein encoded by the gene mutated in congenital dyserythropoietic anemia type I (CDAN1), is cell cycle-regulated

Cited by 32 publications

References 31 publications

Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1α localization in erythroblasts

Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1α localization in erythroblasts

Congenital dyserythropoietic anemia

Clinical aspects and pathogenesis of congenital dyserythropoietic anemias: from morphology to molecular approach

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