共查询到20条相似文献,搜索用时 31 毫秒
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Takashi Moriguchi Mikiko Suzuki Lei Yu Jun Takai Kinuko Ohneda Masayuki Yamamoto 《Molecular and cellular biology》2015,35(5):805-815
GATA1 is a master regulator of erythropoiesis, expression of which is regulated by multiple discrete cis-acting elements. In this study, we examine the activity of a promoter-proximal double GATA (dbGATA) motif, using a Gata1 bacterial artificial chromosome (BAC)-transgenic green fluorescent protein (GFP) reporter (G1BAC-GFP) mouse system. Deletion of the dbGATA motif led to significant reductions in GFP expression in hematopoietic progenitors, while GFP expression was maintained in erythroblasts. Consistently, in mice with a germ line deletion of the dbGATA motif (Gata1ΔdbGATA mice), GATA1 expression in progenitors was significantly decreased. The suppressed GATA1 expression was associated with a compensatory increase in GATA2 levels in progenitors. When we crossed Gata1ΔdbGATA mice with Gata2 hypomorphic mutant mice (Gata2fGN/fGN mice), the Gata1ΔdbGATA::Gata2fGN/fGN compound mutant mice succumbed to a significant decrease in the progenitor population, whereas both groups of single mutant mice maintained progenitors and survived to adulthood, indicating the functional redundancy between GATA1 and GATA2 in progenitors. Meanwhile, the effects of the dbGATA site deletion on Gata1 expression were subtle in erythroblasts, which showed increased GATA1 binding and enhanced accumulation of active histone marks around the 1st-intron GATA motif of the ΔdbGATA locus. These results thus reveal a novel role of the dbGATA motif in the maintenance of Gata1 expression in hematopoietic progenitors and a functional compensation between the dbGATA site and the 1st-intron GATA motif in erythroblasts. 相似文献
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Tadahiro Kumagai Minesuke Yokoyama Tadashi Shinkai 《Biochemical and biophysical research communications》2009,379(2):456-27224
The β-1,4-galactosyltransferase (β-1,4-GalT) V whose human and mouse genes were cloned by us has been suggested to be involved in the biosynthesis of N-glycans and O-glycans, and lactosylceramide. To determine its biological function, β-1,4-GalT V (B4galt5) mutant mice obtained by a gene trap method were analyzed. Analysis of pre- and post-implantation embryos revealed that the B4galt5−/− mice die by E10.5 while B4galt5+/− mice were born and grown normally. Histological study showed that most tissues are formed in B4galt5−/− embryos but their appearance at E10.5 is close to that of B4galt5+/− embryos at E9.0-9.5. The results indicate that the growth is delayed by one to one and half day in B4galt5−/− embryos when compared to B4galt5+/− embryos, which results in early death of the embryos by E10.5, probably due to hematopoietic and/or placental defects. 相似文献
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GATA4 is expressed early in the developing heart where it plays a key role in regulating the expression of genes encoding myocardial
contractile proteins. Gene mutations in the human GATA4 have been implicated in various congenital heart defects (CHD), including atrial septal defect (ASD). Although ASD is the
third most common CHD in humans, it is generally rare in dogs and cats. There is also no obvious predilection for ASD in dogs
and cats, based on sex or breed. However, among dogs, the incidence rate of ASD is relatively high in Samoyeds and Doberman
Pinschers, where its inheritance and genetic aetiology are not well understood. In this study, we identified and investigated
the genetic aetiology of an ASD affected family in a pure breed dog population. Although the GATA4 gene was screened, we did not find any mutations that would result in the alteration of the coding sequence and hence, the
predicted GATA4 structure and function. Although the aetiology of ASD is multifactorial, our findings indicate that GATA4 may not be responsible for the ASD in the dogs used in this study. However, this does not eliminate GATA4 as a candidate for ASD in other dog breeds. 相似文献
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Liao J Aggarwal VS Nowotschin S Bondarev A Lipner S Morrow BE 《Developmental biology》2008,316(2):524-537
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Kinuko Ohneda Takashi Moriguchi Shin'ya Ohmori Yasushi Ishijima Hironori Satoh Sjaak Philipsen Masayuki Yamamoto 《Molecular and cellular biology》2014,34(10):1812-1826
Although previous studies have shown that GATA1 is required for mast cell differentiation, the effects of the complete ablation of GATA1 in mast cells have not been examined. Using conditional Gata1 knockout mice (Gata1−/y), we demonstrate here that the complete ablation of GATA1 has a minimal effect on the number and distribution of peripheral tissue mast cells in adult mice. The Gata1−/y bone marrow cells were capable of differentiating into mast cells ex vivo. Microarray analyses showed that the repression of GATA1 in bone marrow mast cells (BMMCs) has a small impact on the mast cell-specific gene expression in most cases. Interestingly, however, the expression levels of mast cell tryptases in the mouse chromosome 17A3.3 were uniformly reduced in the GATA1 knockdown cells, and GATA1 was found to bind to a 500-bp region at the 5′ end of this locus. Revealing a sharp contrast to that observed in the Gata1-null BMMCs, GATA2 deficiency resulted in a significant loss of the c-Kit+ FcεRIα+ mast cell fraction and a reduced expression of several mast cell-specific genes. Collectively, GATA2 plays a more important role than GATA1 in the regulation of most mast cell-specific genes, while GATA1 might play specific roles in mast cell functions. 相似文献
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GATA6 is essential for embryonic development of the liver but dispensable for early heart formation 总被引:8,自引:0,他引:8
Zhao R Watt AJ Li J Luebke-Wheeler J Morrisey EE Duncan SA 《Molecular and cellular biology》2005,25(7):2622-2631
Several lines of evidence suggest that GATA6 has an integral role in controlling development of the mammalian liver. Unfortunately, this proposal has been impossible to address directly because mouse embryos lacking GATA6 die during gastrulation. Here we show that the early embryonic deficiency associated with GATA6-knockout mice can be overcome by providing GATA6-null embryos with a wild-type extraembryonic endoderm with the use of tetraploid embryo complementation. Analysis of rescued Gata6-/- embryos revealed that, although hepatic specification occurs normally, the specified cells fail to differentiate and the liver bud does not expand. Although GATA6 is expressed in multiple tissues that impact development of the liver, including the heart, septum transversum mesenchyme, and vasculature, all are relatively unaffected by loss of GATA6, which is consistent with a cell-autonomous requirement for GATA6 during hepatogenesis. We also demonstrate that a closely related GATA factor, GATA4, is expressed transiently in the prehepatic endoderm during hepatic specification and then lost during expansion of the hepatic primordium. Our data support the proposal that GATA4 and GATA6 are functionally redundant during hepatic specification but that GATA6 alone is available for liver bud growth and commitment of the endoderm to a hepatic cell fate. 相似文献
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Ramegowda S Kumar A Savitha MR Krishnamurthy B Doddaiah N Ramachandra NB 《Indian journal of human genetics》2007,13(1):30-32