title: Klf1 affects DNase II-alpha expression in the central macrophage of a fetal liver erythroblastic island: a non-cell-autonomous role in definitive erythropoiesis.
abstract: 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.
authors.affiliation: Istituto di Ricerca Genetica e Biomedica del Consiglio Nazionale delle Ricerche, Cagliari, Sardinia, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Porcu
authors.forename: Maria F
authors.initials: MF
authors.lastname: Manchinu
authors.forename: Maria F
authors.initials: MF
authors.lastname: Marongiu
authors.forename: Valeria
authors.initials: V
authors.lastname: Sogos
authors.forename: Daniela
authors.initials: D
authors.lastname: Poddie
authors.forename: Isadora
authors.initials: I
authors.lastname: Asunis
authors.forename: Loredana
authors.initials: L
authors.lastname: Porcu
authors.forename: Maria G
authors.initials: MG
authors.lastname: Marini
authors.forename: Paolo
authors.initials: P
authors.lastname: Moi
authors.forename: Antonio
authors.initials: A
authors.lastname: Cao
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
authors.forename: Maria S
authors.initials: MS
authors.lastname: Ristaldi
mesh_terms: D000818:Animals; D002460:Cell Line; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D004900:Erythroblasts / Q000166:cytology / Q000502:physiology*; D004920:Erythropoiesis / Q000502:physiology*; D005333:Fetus / Q000033:anatomy & histology*; D006801:Humans; D016899:Interferon-beta / Q000235:genetics; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
chemical_list: D051741:Kruppel-Like Transcription Factors; D034741:RNA, Small Interfering; C080774:erythroid Kruppel-like factor; D016899:Interferon-beta; D004706:Endodeoxyribonucleases; C019329:deoxyribonuclease II