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 mDom(DeltaN/DeltaN)). The mDom(DeltaN/DeltaN) 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 mDom(DeltaN/DeltaN) 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 mDom(DeltaN/DeltaN) 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.
Ueda
Takeshi
T
Laboratory of Genetics (B-3), Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Japan Science and Technology Corporation, Osaka, Japan.
Watanabe-Fukunaga
Rie
R
Ogawa
Hironori
H
Fukuyama
Hidehiro
H
Higashi
Yujiro
Y
Nagata
Shigekazu
S
Fukunaga
Rikiro
R
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000502:physiology*; D004265:DNA Helicases; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins; D004920:Erythropoiesis / Q000235:genetics / Q000502:physiology; D005260:Female; D047109:Fetal Development / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015017:Yolk Sac / Q000378:metabolism
D017931:DNA Primers; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; C499332:Ep400 protein, mouse