Subject(s)
Cell Transformation, Neoplastic/genetics , Chromatin/chemistry , Genes, Tumor Suppressor , Acetylation , Animals , Chromatin/metabolism , Chromosomal Proteins, Non-Histone , DNA Methylation , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Heterochromatin/chemistry , Histones/chemistry , Humans , Methylation , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Nucleosomes/chemistry , Phosphorylation , SMARCB1 Protein , Signal Transduction , Trans-Activators/genetics , Trans-Activators/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
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.
