Journal Article

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

Xiao, Hua, Southon, Eileen, Tessarollo, Lino, Sharov, Alexei A., Piao, Yulan, Zhang, Ying E., Yamaguchi, Terry P., Ko, Minoru S. H., Matta, Jennifer, Kuehn, Michael R., Landry, Joseph, Sharova, Lioudmila V., Wu, Carl

2008

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 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