Brg1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for myeloid differentiation to granulocytes.

Many mammalian SWI/SNF complexes use Brahma-related gene 1 (Brg1) as a catalytic subunit to remodel nucleosomes for transcription regulation. In several mesenchymal cells and tissues, expression of a defective Brg1 protein negates the normal activity of the SWI/SNF complex and delays or blocks differentiation. To investigate the role of SWI/SNF complexes during myelopoiesis, we stably expressed a dominant negative (dn) Brg1 mutant in the myeloid lineage.

Loss of the INI1 tumor suppressor does not impair the expression of multiple BRG1-dependent genes or the assembly of SWI/SNF enzymes.

The INI1/hSNF5 tumor suppressor is an integral component of mammalian SWI/SNF chromatin remodeling enzymes that contain SNF2 family ATPases BRM (Brahma) or BRG1 (Brahma Related Gene 1) and that contribute to the regulation of many genes. Genetic studies of yeast SWI/SNF enzyme revealed similar phenotypes when single or multiple components of the enzyme were deleted, indicating a requirement for each subunit. To address the contribution of INI1 in the regulation of SWI/SNF-dependent genes in mammalian cells, we examined the expression of multiple BRG1-dependent, constitutively expressed genes in INI1-deficient cancer cell lines.