TY - JOUR TI - SETD2 is essential for terminal differentiation of erythroblasts during fetal erythropoiesis AU - Li, Yali AU - Tang, Huayuan AU - Chen, Fengling AU - Chen, Jiewen AU - Wang, Hong AU - Chen, Zee AU - Duan, Yaoyun AU - Wang, Xinru AU - Li, Li AU - Ouyang, Kunfu T2 - Biochemical and Biophysical Research Communications AB - SET domain-containing 2 (SETD2), the primary methyltransferase for histone 3 lysine-36 trimethylation (H3K36me3) in mammals, is associated with many hematopoietic diseases when mutated. Previous works have emphasized its role in maintaining adult hematopoietic stem cells or tumorigenesis, however, whether and how SETD2 regulates erythropoiesis during embryonic development is relatively unexplored. In this study, using a conditional SETD2 knockout (KO) mouse model, we reveal that SETD2 plays an essential role in fetal erythropoiesis. Loss of Setd2 in hematopoietic cells ablates H3K36me3, and leads to anemia with a significant decrease in erythroid cells in the peripheral blood at E18.5. This is due to impaired erythroblast differentiation in both spleen and liver. We also find increased proportions of nucleated erythrocytes in the blood of Setd2 KO embryos. Lastly, we ascribe embryonic erythropoiesis-related genes Vegfc, Vegfr3, and Prox1, as likely downstream targets of SETD2 regulation. Our study reveals a critical role of SETD2 in fetal erythropoiesis that precedes adult hematopoiesis, and provide unique insights into the defects in erythroid lineages, such as anemia. DA - 2021/05/07/ PY - 2021 DO - 10.1016/j.bbrc.2021.03.040 DP - ScienceDirect VL - 552 SP - 98 EP - 105 J2 - Biochemical and Biophysical Research Communications LA - en SN - 0006-291X UR - https://www.sciencedirect.com/science/article/pii/S0006291X21004228 Y2 - 2021/03/30/17:50:16 KW - Anemia KW - Enucleation KW - Fetal erythropoiesis KW - H3K36me3 KW - SETD2 ER -