Critical role of the p400/mDomino chromatin‐remodeling ATPase in embryonic hematopoiesis
Copyright policy )Critical role of the p400/mDomino chromatin‐remodeling ATPase in embryonic hematopoiesis
The SWI2/SNF2 family ATPase, p400/mDomino, is a core subunit of a large chromatin‐remodeling complex, and is currently suggested to play a unique function in histone variant exchange, a process by which chromatin structure is altered. Here, we investigated the role of p400/mDomino in mammalian development by generating mutant mice with a targeted deletion of the N‐terminal domain of p400/mDomino (referred to as mDomΔN/ΔN). The mDomΔN/ΔN mice died on embryonic day 11.5 (E11.5), and displayed an anemic appearance and slight deformity of the neural tube. DNA microarray and quantitative RT‐PCR analyses revealed that all of the embryonic globin genes and a globin chaperone gene were poorly expressed in the mDomΔN/ΔN embryo and yolk sac on E8.5, indicating that primitive erythropoiesis was impaired. A hematopoietic colony assay indicated that the hematopoietic activity of the yolk sac was significantly blocked in the mutant mice. We also found that the expression of a limited set of Hox genes, including Hoxa7, Hoxa9 and Hoxb9, was drastically enhanced in the mDomΔN/ΔN yolk sacs. These results suggest that p400/mDomino plays a critical role in embryonic hematopoiesis by regulating the expression of developmentally essential genes such as those in the Hox gene cluster.
- Osaka University Japan
Adenosine Triphosphatases, Male, Mice, Knockout, Mice, Inbred ICR, Base Sequence, DNA Helicases, Genes, Homeobox, Gene Expression Regulation, Developmental, Chromatin Assembly and Disassembly, Mice, Mutant Strains, Hematopoiesis, DNA-Binding Proteins, Fetal Development, Mice, Animals, Erythropoiesis, Female, In Situ Hybridization, DNA Primers, Oligonucleotide Array Sequence Analysis
Adenosine Triphosphatases, Male, Mice, Knockout, Mice, Inbred ICR, Base Sequence, DNA Helicases, Genes, Homeobox, Gene Expression Regulation, Developmental, Chromatin Assembly and Disassembly, Mice, Mutant Strains, Hematopoiesis, DNA-Binding Proteins, Fetal Development, Mice, Animals, Erythropoiesis, Female, In Situ Hybridization, DNA Primers, Oligonucleotide Array Sequence Analysis
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