Document Detail

Klf1 affects DNase II-alpha expression in the central macrophage of a fetal liver erythroblastic island: a non-cell-autonomous role in definitive erythropoiesis.
MedLine Citation:
PMID:  21807894     Owner:  NLM     Status:  MEDLINE    
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.
Susanna Porcu; Maria F Manchinu; Maria F Marongiu; Valeria Sogos; Daniela Poddie; Isadora Asunis; Loredana Porcu; Maria G Marini; Paolo Moi; Antonio Cao; Frank Grosveld; Maria S Ristaldi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-08-01
Journal Detail:
Title:  Molecular and cellular biology     Volume:  31     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-12     Completed Date:  2011-12-12     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4144-54     Citation Subset:  IM    
Istituto di Ricerca Genetica e Biomedica del Consiglio Nazionale delle Ricerche, Cagliari, Sardinia, Italy.
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MeSH Terms
Cell Line
Endodeoxyribonucleases / genetics,  metabolism*
Erythroblasts / cytology,  physiology*
Erythropoiesis / physiology*
Fetus / anatomy & histology*
Interferon-beta / genetics
Kruppel-Like Transcription Factors / genetics,  metabolism*
Liver / cytology,  metabolism*
Macrophages / cytology,  metabolism
Mice, Inbred C57BL
Mice, Knockout
Promoter Regions, Genetic
RNA, Small Interfering / genetics,  metabolism
Reg. No./Substance:
0/Kruppel-Like Transcription Factors; 0/RNA, Small Interfering; 0/erythroid Kruppel-like factor; 77238-31-4/Interferon-beta; EC 3.1.-/Endodeoxyribonucleases; EC II

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