Abstract
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.