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Publication : Klf1 affects DNase II-alpha expression in the central macrophage of a fetal liver erythroblastic island: a non-cell-autonomous role in definitive erythropoiesis.

First Author  Porcu S Year  2011
Journal  Mol Cell Biol Volume  31
Issue  19 Pages  4144-54
PubMed ID  21807894 Mgi Jnum  J:175864
Mgi Id  MGI:5287547 Doi  10.1128/MCB.05532-11
Citation  Porcu S, et al. (2011) Klf1 Affects DNase II-Alpha Expression in the Central Macrophage of a Fetal Liver Erythroblastic Island: a Non-Cell-Autonomous Role in Definitive Erythropoiesis. Mol Cell Biol 31(19):4144-54
abstractText  A key regulatory gene in definitive erythropoiesis is the erythroid Kruppel-like factor (Eklf or Klf1). Klf1 knockout (KO) mice die in utero due to severe anemia, while residual circulating red blood cells retain their nuclei. Dnase2a is another critical gene in definitive erythropoiesis. Dnase2a KO mice are also affected by severe anemia and die in utero. DNase II-alpha is expressed in the central macrophage of erythroblastic islands (CMEIs) of murine fetal liver. Its main role is to digest the DNA of the extruded nuclei of red blood cells during maturation. Circulating erythrocytes retain their nuclei in Dnase2a KO mice. Here, we show that Klf1 is expressed in CMEIs and that it binds and activates the promoter of Dnase2a. We further show that Dnase2a is severely downregulated in the Klf1 KO fetal liver. We propose that this downregulation of Dnase2a in the CMEI contributes to the Klf1 KO phenotype by a non-cell-autonomous mechanism.
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