The murine SNF5/INI1 chromatin remodeling factor is essential for embryonic development and tumor suppression.
The assembly of eukaryotic DNA into nucleosomes and derived higher order structures constitutes a barrier for transcription, replication and repair. A number of chromatin remodeling complexes, as well as histone acetylation, were shown to facilitate gene activation. To investigate the function of two closely related mammalian SWI/SNF complexes in vivo, we inactivated the murine SNF5/INI1 gene, a common subunit of these two complexes. Mice lacking SNF5 protein stop developing at the peri-implantation stage, showing that the SWI/SNF complex is essential for early development and viability of early embryonic cells. Furthermore, heterozygous mice develop nervous system and soft tissue sarcomas. In these tumors the wild-type allele was lost, providing further evidence that SNF5 functions as a tumor suppressor gene in certain cell types.
Unité des Virus Oncogènes, CNRS URA 1644, Institut Pasteur, Paris, France.
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A
Klochendler-Yeivin
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L
Fiette
J
J
Barra
C
C
Muchardt
C
C
Babinet
M
M
Yaniv
D000483:Alleles; D000818:Animals; D017209:Apoptosis; D001755:Blastocyst / Q000378:metabolism; D015139:Blotting, Southern; D016923:Cell Death; D002868:Chromosomal Proteins, Non-Histone; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D004622:Embryo, Mammalian / Q000502:physiology*; D005091:Exons; D005260:Female; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007763:Lac Operon; D019656:Loss of Heterozygosity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D016296:Mutagenesis; D009369:Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction; D000071796:SMARCB1 Protein; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014746:Vimentin / Q000096:biosynthesis; D001616:beta-Galactosidase / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513265:Smarcb1 protein, mouse; D014157:Transcription Factors; D014746:Vimentin; D001616:beta-Galactosidase