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.
Pubmed ID: 11263494 RIS Download
Alleles | Animals | Apoptosis | Blastocyst | Blotting, Southern | Cell Death | Chromosomal Proteins, Non-Histone | Crosses, Genetic | DNA-Binding Proteins | Embryo, Mammalian | Exons | Female | Gene Expression Regulation | Gene Expression Regulation, Developmental | Genetic Predisposition to Disease | Genotype | Heterozygote | Immunohistochemistry | In Situ Nick-End Labeling | Lac Operon | Loss of Heterozygosity | Male | Mice | Mice, Inbred C57BL | Models, Genetic | Mutagenesis | Neoplasms | Polymerase Chain Reaction | SMARCB1 Protein | Stem Cells | Time Factors | Transcription Factors | Transcription, Genetic | Transcriptional Activation | Vimentin | beta-Galactosidase