The role of EKLF in human β-globin gene competition.
Gene Expression Regulation, Developmental
0 (DNA-Binding Proteins)
0 (RNA, Messenger)
0 (Transcription Factors)
0 (erythroid Kruppel-like factor)
EC 18.104.22.168 (Deoxyribonuclease I)
In Situ Hybridization, Fluorescence
Promoter Regions (Genetics)
RNA, Messenger/isolation & purification
Support, Non-U.S. Gov't
Genes & Development, 10, 2894 - 2902
Rok publikacji :
Opis pliku :
Numer akcesji :
textabstractWe have investigated the role of erythroid Kruppel-like factor (EKLF) in expression of the human beta-globin genes in compound EKLF knockout/human beta-locus transgenic mice. EKLF affects only the adult mouse beta-globin genes in homozygous knockout mice; heterozygous mice are unaffected. Here we show that EKLF knockout mice express the human epsilon and gamma-globin genes normally in embryonic red cells. However, fetal liver erythropoiesis, which is marked by a period of gamma- and beta-gene competition in which the genes are alternately transcribed, exhibits an altered ratio of gamma- to beta-gene transcription. EKLF heterozygous fetal livers display a decrease in the number of transcriptionally active beta genes with a reciprocal increase in the number of transcriptionally active gamma genes. beta-Gene transcription is absent in homozygous knockout fetuses with coincident changes in chromatin structure at the beta promoter. There is a further increase in the number of transcriptionally active gamma genes and accompanying gamma gene promoter chromatin alterations. These results indicate that EKLF plays a major role in gamma- and beta-gene competition and suggest that EKLF is important in stabilizing the interaction between the Locus Control Region and the beta-globin gene. In addition, these findings provide further evidence that developmental modulation of globin gene expression within individual cells is accomplished by altering the frequency and/or duration of transcriptional periods of a gene rather than changing the rate of transcription.