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Publication : TRIM28 is essential for erythroblast differentiation in the mouse.

First Author  Hosoya T Year  2013
Journal  Blood Volume  122
Issue  23 Pages  3798-807
PubMed ID  24092935 Mgi Jnum  J:204593
Mgi Id  MGI:5532865 Doi  10.1182/blood-2013-04-496166
Citation  Hosoya T, et al. (2013) TRIM28 is essential for erythroblast differentiation in the mouse. Blood 122(23):3798-807
abstractText  In previous mass spectrometry and coimmune precipitation studies, we identified tripartite motif-containing 28 (TRIM28; also known as transcriptional intermediary factor1beta and Kruppel-associated box-associated protein-1) as a cofactor that specifically copurified with an NR2C1/NR2C2 (TR2/TR4) orphan nuclear receptor heterodimer that previous studies had implicated as an embryonic/fetal beta-type globin gene repressor. TRIM28 has been characterized as a transcriptional corepressor that can associate with many different transcription factors and can play functional roles in multiple tissues and cell types. Here, we tested the contribution of TRIM28 to globin gene regulation and erythropoiesis using a conditional loss-of-function in vivo model. We discovered that Trim28 genetic loss in the adult mouse leads to defective immature erythropoiesis in the bone marrow and consequently to anemia. We further found that TRIM28 controls erythropoiesis in a cell-autonomous manner by inducibly deleting Trim28 exclusively in hematopoietic cells. Finally, in the absence of TRIM28, we observed increased apoptosis as well as diminished expression of multiple erythroid transcription factors and heme biosynthetic enzymes in immature erythroid cells. Thus, TRIM28 is essential for the cell-autonomous development of immature erythroblasts in the bone marrow.
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