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Haem‐regulated eIF2α kinase is necessary for adaptive gene expression in erythroid precursors under the stress of iron deficiency
Author(s) -
Liu Sijin,
Bhattacharya Sanchita,
Han Anping,
Suragani Rajasekhar N. V. S.,
Zhao Wanting,
Fry Rebecca C.,
Chen JaneJane
Publication year - 2008
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2008.07293.x
Subject(s) - erythropoiesis , iron deficiency , gata1 , gene expression , biology , erythroblast , ineffective erythropoiesis , gene , ferritin , transferrin receptor , kinase , microarray analysis techniques , transferrin , microbiology and biotechnology , medicine , endocrinology , anemia , biochemistry
Summary Haem‐regulated eIF2α kinase (HRI) is essential for the regulation of globin gene translation and the survival of erythroid precursors in iron/haem deficiency. This study found that that in iron deficiency, fetal definitive erythropoiesis is inhibited at the basophilic erythroblast stage with increased proliferation and elevated apoptosis. This hallmark of ineffective erythropoiesis is more severe in HRI deficiency. Microarray gene profiling analysis showed that HRI was required for adaptive gene expression in erythroid precursors during chronic iron deficiency. The number of genes with expression affected more than twofold increased, from 213 in iron deficiency and 73 in HRI deficiency, to 3135 in combined iron and HRI deficiencies. Many of these genes are regulated by Gata1 and Fog1. We demonstrate for the first time that Gata1 expression in developing erythroid precursors is decreased in iron deficiency, and is decreased further in combined iron and HRI deficiencies. Additionally, Fog1 expression is decreased in combined deficiencies, but not in iron or HRI deficiency alone. Our results indicate that HRI confers adaptive gene expression in developing erythroblasts during iron deficiency through maintaining Gata1/Fog1 expression.