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

PLoS genetics | Oct 31, 2008

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.

Pubmed ID: 18974875 RIS Download

Mesh terms: Adenosine Triphosphatases | Animals | Antigens, Nuclear | Cell Differentiation | Chromatin Assembly and Disassembly | Chromosomal Proteins, Non-Histone | DNA Helicases | DNA-Binding Proteins | Embryo, Mammalian | Embryonic Development | Embryonic Stem Cells | Endoderm | Left-Right Determination Factors | Mice | Mice, Knockout | Mutation | Nerve Tissue Proteins | Oligonucleotide Array Sequence Analysis | Smad Proteins | Transcription Factors

Research resources used in this publication

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Data used in this publication

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Associated grants

  • Agency: NCI NIH HHS, Id: N01CO12400
  • Agency: Intramural NIH HHS, Id: Z01 BC010419-08
  • Agency: NCI NIH HHS, Id: N01-CO-12400

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International Gene Trap Consortium

A public library of mutated murine ES cell lines generated by its members around the world that are publicly available on a non-collaborative basis for nominal handling fees. Each member has their own means of distributing their cell lines. A link is provided to the respective member's cell line provider on each cell line page in the Sequence Tag Information section in the Availability line. The cell lines can be obtained on a non-collaborative basis by scientists interested in generating reporter-tagged, loss-of-function mutations in mice. In addition to loss of function, newer gene trap vectors offer a variety of post-insertional modification strategies to allow for the generation of other experimental alleles. The cooperative goal of the IGTC is to generate an international resource representing all or most genes in the mouse genome, and to provide the bioinformatics and logistical support to make the resource valuable and available to scientists. Researchers can search and browse the IGTC database for cell lines of interest using accession numbers or IDs, keywords, sequence data, tissue expression profiles and biological pathways. By using gene trap cell lines found on the IGTC site, researchers can save the time and expense of targeting a gene for knockout. Researchers can find trapped genes of interest on the IGTC website, and order cell lines for the generation of mutant mice through blastocyst injection. Consortium members include: BayGenomics (USA), Centre for Modelling Human Disease (Toronto, Canada), Embryonic Stem Cell Database (University of Manitoba, Canada), Exchangeable Gene Trap Clones (Kumamoto University, Japan), German Gene Trap Consortium provider (Germany), Sanger Institute Gene Trap Resource (Cambridge, UK), Soriano Lab Gene Trap Resource (Mount Sinai School of Medicine, New York, USA), Texas Institute for Genomic Medicine - TIGM (USA), TIGEM-IRBM Gene Trap (Naples, Italy)

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Database for Annotation Visualization and Integrated Discovery

A database which provides a comprehensive set of functional annotation tools for investigators to understand biological meaning behind large list of genes. For any given gene list, DAVID tools are able to perform a variety of actions such as identifying enriched biological themes (particularly GO terms), discovering enriched functional-related gene groups, clustering redundant annotation terms, and visualizing genes on BioCarta and KEGG pathway maps.

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BayGenomics

THIS RESOURCE IS NO LONGER IN SERVICE, documented August 29, 2016. The BayGenomics gene-trap resource provides researchers with access to thousands of mouse embryonic stem (ES) cell lines harboring characterized insertional mutations in both known and novel genes. The major goal of BayGenomics is to identify genes relevant to cardiovascular and pulmonary disease.

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NIA Array Analysis

Data analysis server / software designed to test statistical significance of gene microarray data, visualize the results, and provide links to clone information and gene index. Several public datasets are also available.

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Cold Spring Harbor Laboratory

A non-profit, private research and education institution that performs molecular and genetic research used to generate methods for better diagnostics and treatments for cancer and neurological diseases. This lab has done specific research of cancer-causing genes and their respective signaling pathways. They have also researched mutations and structural variations of the human genome that could cause neurodevelopmental and neurodegenerative illnesses such as autism, schizophrenia, and Alzheimer's and Parkinson's diseases. This laboratory is also involved in plant genetics and quantitative biology.

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