Essential Role of Chromatin Remodeling Protein Bptf in Early Mouse Embryos and Embryonic Stem Cells

We have characterized the biological functions of the chromatin remodeling protein Bptf (Bromodomain PHD-finger Transcription Factor), the largest subunit of NURF (Nucleosome Remodeling Factor) in a mammal. Bptf mutants manifest growth defects at the post-implantation stage and are reabsorbed by E8....

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Vydáno v:	PLoS genetics Ročník 4; číslo 10; s. e1000241
Hlavní autoři:	Landry, Joseph, Sharov, Alexei A., Piao, Yulan, Sharova, Lioudmila V., Xiao, Hua, Southon, Eileen, Matta, Jennifer, Tessarollo, Lino, Zhang, Ying E., Ko, Minoru S. H., Kuehn, Michael R., Yamaguchi, Terry P., Wu, Carl
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 01.10.2008 Public Library of Science (PLoS)
Témata:	Adenosine Triphosphatases - metabolism Animals Antigens, Nuclear - genetics Antigens, Nuclear - metabolism ATPases Associated with Diverse Cellular Activities Biochemistry/Transcription and Translation Cell Biology/Cell Growth and Division Cell Biology/Cell Signaling Cell Biology/Developmental Molecular Mechanisms Cell Biology/Gene Expression Cell Biology/Nuclear Structure and Function Cell Differentiation Chromatin Chromatin Assembly and Disassembly - physiology Chromosomal Proteins, Non-Histone - metabolism Developmental Biology/Cell Differentiation Developmental Biology/Developmental Molecular Mechanisms Developmental Biology/Embryology Developmental Biology/Molecular Development Developmental Biology/Morphogenesis and Cell Biology Developmental Biology/Pattern Formation Developmental Biology/Stem Cells DNA Helicases - metabolism DNA-Binding Proteins - metabolism Embryo, Mammalian - metabolism Embryonic Development Embryonic Stem Cells - cytology Embryonic Stem Cells - physiology Embryos Endoderm - embryology Genetics and Genomics/Animal Genetics Genetics and Genomics/Epigenetics Left-Right Determination Factors - metabolism Mice Mice, Knockout Mutation Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Oligonucleotide Array Sequence Analysis Proteins Smad Proteins - metabolism Stem cells Transcription Factors - genetics Transcription Factors - metabolism
ISSN:	1553-7404, 1553-7390, 1553-7404
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Shrnutí:	We have characterized the biological functions of the chromatin remodeling protein Bptf (Bromodomain PHD-finger Transcription Factor), the largest subunit of NURF (Nucleosome Remodeling Factor) in a mammal. Bptf mutants manifest growth defects at the post-implantation stage and are reabsorbed by E8.5. Histological analyses of lineage markers show that Bptf(-/-) embryos implant but fail to establish a functional distal visceral endoderm. Microarray analysis at early stages of differentiation has identified Bptf-dependent gene targets including homeobox transcriptions factors and genes essential for the development of ectoderm, mesoderm, and both definitive and visceral endoderm. Differentiation of Bptf(-/-) embryonic stem cell lines into embryoid bodies revealed its requirement for development of mesoderm, endoderm, and ectoderm tissue lineages, and uncovered many genes whose activation or repression are Bptf-dependent. We also provide functional and physical links between the Bptf-containing NURF complex and the Smad transcription factors. These results suggest that Bptf may co-regulate some gene targets of this pathway, which is essential for establishment of the visceral endoderm. We conclude that Bptf likely regulates genes and signaling pathways essential for the development of key tissues of the early mouse embryo.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: JL AAS HX MSHK TPY CW. Performed the experiments: JL YP LVS EAS JM. Analyzed the data: JL AAS. Contributed reagents/materials/analysis tools: JL LT YEZ MSHK MRK TPY CW. Wrote the paper: JL AAS MRK TPY CW.
ISSN:	1553-7404 1553-7390 1553-7404
DOI:	10.1371/journal.pgen.1000241