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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Published in:PLoS genetics Vol. 4; no. 10; p. e1000241
Main Authors: 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
Format: Journal Article
Language:English
Published: United States Public Library of Science 01.10.2008
Public Library of Science (PLoS)
Subjects:
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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Summary: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.
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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