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Krüppel-Like Factor 1 (KLF1), KLF2, and Myc Control a Regulatory Network Essential for Embryonic Erythropoiesis
- Publication Year :
- 2012
- Publisher :
- American Society for Microbiology, 2012.
-
Abstract
- The Krüppel-like factor 1 (KLF1) and KLF2 positively regulate embryonic β-globin expression and have additional overlapping roles in embryonic (primitive) erythropoiesis. KLF1(-/-) KLF2(-/-) double knockout mice are anemic at embryonic day 10.5 (E10.5) and die by E11.5, in contrast to single knockouts. To investigate the combined roles of KLF1 and KLF2 in primitive erythropoiesis, expression profiling of E9.5 erythroid cells was performed. A limited number of genes had a significantly decreasing trend of expression in wild-type, KLF1(-/-), and KLF1(-/-) KLF2(-/-) mice. Among these, the gene for Myc (c-Myc) emerged as a central node in the most significant gene network. The expression of the Myc gene is synergistically regulated by KLF1 and KLF2, and both factors bind the Myc promoters. To characterize the role of Myc in primitive erythropoiesis, ablation was performed specifically in mouse embryonic proerythroblast cells. After E9.5, these embryos exhibit an arrest in the normal expansion of circulating red cells and develop anemia, analogous to KLF1(-/-) KLF2(-/-) embryos. In the absence of Myc, circulating erythroid cells do not show the normal increase in α- and β-like globin gene expression but, interestingly, have accelerated erythroid cell maturation between E9.5 and E11.5. This study reveals a novel regulatory network by which KLF1 and KLF2 regulate Myc to control the primitive erythropoietic program.
- Subjects :
- Male
Erythroblasts
Genes, myc
Kruppel-Like Transcription Factors
KLF1
beta-Globins
Biology
Mice
alpha-Globins
Pregnancy
Animals
Erythropoiesis
Gene Regulatory Networks
RNA, Messenger
Promoter Regions, Genetic
Molecular Biology
Gene
Gene knockout
DNA Primers
Mice, Knockout
Base Sequence
Gene Expression Profiling
Gene Expression Regulation, Developmental
Promoter
Cell Biology
Articles
Embryonic stem cell
Molecular biology
Gene expression profiling
KLF2
Female
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....a809353a00b5e113fa88808cc6a17a4e