TY - JOUR
T1 - TRIM28 is essential for erythroblast differentiation in the mouse
AU - Hosoya, Tomonori
AU - Clifford, Mary
AU - Losson, Régine
AU - Tanabe, Osamu
AU - Engel, James Douglas
N1 - Funding Information:
This work was supported by National Institutes of Health grants HL24415 and HL114368 (J.D.E.) and was supported in part by a fellowship from the Astellas Foundation for Research on Metabolic Disorders (T.H.).The research was also supported in part by the National Cancer Institute through the University of Michigan’s Cancer Center Support Grant (P30 CA046592) and the use of the following cores: Flow Cytometry, Morphology, Microscopy and Image Analysis Laboratory, Experimental Irradiation, and Sequencing.
Funding Information:
The authors thank Kevin Lane, Carmen Yu, and the Unit for Laboratory Animal Medicine at the University of Michigan for experimental support and excellent animal care. The authors also thank members of the Engel Laboratory for advice and discussion. This work was supported by National Institutes of Health grants HL24415 and HL114368 (J.D.E.) and was supported in part by a fellowship from the Astellas Foundation for Research on Metabolic Disorders (T.H.).The research was also supported in part by the National Cancer Institute through the University of Michigan’s Cancer Center Support Grant (P30 CA046592) and the use of the following cores: Flow Cytometry, Morphology, Microscopy and Image Analysis Laboratory, Experimental Irradiation, and Sequencing.
Publisher Copyright:
© 2013 by The American Society of Hematology.
PY - 2013
Y1 - 2013
N2 - In previous mass spectrometry and coimmune precipitation studies, we identified tripartite motif-containing 28 (TRIM28; also known as transcriptional intermediary factor1β and Krüppel-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 β-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.
AB - In previous mass spectrometry and coimmune precipitation studies, we identified tripartite motif-containing 28 (TRIM28; also known as transcriptional intermediary factor1β and Krüppel-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 β-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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U2 - 10.1182/blood-2013-04-496166
DO - 10.1182/blood-2013-04-496166
M3 - Article
C2 - 24092935
AN - SCOPUS:84891081961
VL - 122
SP - 3798
EP - 3807
JO - Blood
JF - Blood
SN - 0006-4971
IS - 23
ER -