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Essential role of chromatin remodeling protein Bptf in early mouse embryos and embryonic stem cells.

Landry J, Sharov AA, Piao Y, Sharova LV, Xiao H, Southon E, Matta J, Tessarollo L, Zhang YE, Ko MS, Kuehn MR, Yamaguchi TP, Wu C - PLoS Genet. (2008)

Bottom Line: 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.We conclude that Bptf likely regulates genes and signaling pathways essential for the development of key tissues of the early mouse embryo.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Biochemistry and Molecular Cell Biology, National Cancer Institute, National Institutes of Heath, Bethesda, MD, USA. landrjos@mail.nih.gov

ABSTRACT
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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Analysis of Bptf knockout mouse embryonic stem cells shows severe defects in gene expression during embryoid differentiation.Relative expression of developmental markers during an embryoid body differentiation time course. The expression of many markers of the ectoderm (A), mesoderm (B), and endoderm (C) tissue lineages were severely defective in Bptf mutants during the differentiation time course.
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pgen-1000241-g003: Analysis of Bptf knockout mouse embryonic stem cells shows severe defects in gene expression during embryoid differentiation.Relative expression of developmental markers during an embryoid body differentiation time course. The expression of many markers of the ectoderm (A), mesoderm (B), and endoderm (C) tissue lineages were severely defective in Bptf mutants during the differentiation time course.

Mentions: An analysis of pre-implantation embryos suggested that Bptf mutants specify a functional primitive endoderm and ICM. The primitive endoderm of Bptf mutant embryos was found to express the primitive endoderm markers Gata6, Lefty1, and Hex1 at comparable levels to wild type controls (Figure 3B). The expression of these markers suggests that Bptf mutants are not defective in the differentiation of the primitive endoderm, the precursor of the visceral endoderm of E5.5 and later stage embryos. Consistent with a functional ICM, we observed normal expression of the pluripotency marker Nanog in Bptf mutants compared to controls (Figure 2B). Taken together, these results indicate that Bptf is not required for the specification of the primitive endoderm and the ICM in E4.5 embryos.


Essential role of chromatin remodeling protein Bptf in early mouse embryos and embryonic stem cells.

Landry J, Sharov AA, Piao Y, Sharova LV, Xiao H, Southon E, Matta J, Tessarollo L, Zhang YE, Ko MS, Kuehn MR, Yamaguchi TP, Wu C - PLoS Genet. (2008)

Analysis of Bptf knockout mouse embryonic stem cells shows severe defects in gene expression during embryoid differentiation.Relative expression of developmental markers during an embryoid body differentiation time course. The expression of many markers of the ectoderm (A), mesoderm (B), and endoderm (C) tissue lineages were severely defective in Bptf mutants during the differentiation time course.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2570622&req=5

pgen-1000241-g003: Analysis of Bptf knockout mouse embryonic stem cells shows severe defects in gene expression during embryoid differentiation.Relative expression of developmental markers during an embryoid body differentiation time course. The expression of many markers of the ectoderm (A), mesoderm (B), and endoderm (C) tissue lineages were severely defective in Bptf mutants during the differentiation time course.
Mentions: An analysis of pre-implantation embryos suggested that Bptf mutants specify a functional primitive endoderm and ICM. The primitive endoderm of Bptf mutant embryos was found to express the primitive endoderm markers Gata6, Lefty1, and Hex1 at comparable levels to wild type controls (Figure 3B). The expression of these markers suggests that Bptf mutants are not defective in the differentiation of the primitive endoderm, the precursor of the visceral endoderm of E5.5 and later stage embryos. Consistent with a functional ICM, we observed normal expression of the pluripotency marker Nanog in Bptf mutants compared to controls (Figure 2B). Taken together, these results indicate that Bptf is not required for the specification of the primitive endoderm and the ICM in E4.5 embryos.

Bottom Line: 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.We conclude that Bptf likely regulates genes and signaling pathways essential for the development of key tissues of the early mouse embryo.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Biochemistry and Molecular Cell Biology, National Cancer Institute, National Institutes of Heath, Bethesda, MD, USA. landrjos@mail.nih.gov

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus