Mitotic inactivation of a human SWI/SNF chromatin remodeling complex.

During mitosis, chromatin is condensed into mitotic chromosomes and transcription is inhibited, processes that might be opposed by the chromatin remodeling activity of the SWI/SNF complexes. Brg1 and hBrm, which are components of human SWI/SNF (hSWI/SNF) complexes, were recently shown to be phosphorylated during mitosis. This suggested that phosphorylation might ...
be used as a switch to modulate SWI/SNF activity. Using an epitope-tag strategy, we have purified hSWI/SNF complexes at different stages of the cell cycle, and found that hSWI/SNF was inactive in cells blocked in G2-M. Mitotic hSWI/SNF contained Brg1 but not hBrm, and was phosphorylated on at least two subunits, hSWI3 and Brg1. In vitro, active hSWI/SNF from asynchronous cells can be phosphorylated and inactivated by ERK1, and reactivated by dephosphorylation. hSWI/SNF isolated as cells traversed mitosis regained activity when its subunits were dephosphorylated either in vitro or in vivo. We propose that this transitional inactivation and reactivation of hSWI/SNF is required for formation of a repressed chromatin structure during mitosis and reformation of an active chromatin structure as cells leave mitosis.
Mesh Terms:
Base Sequence, Calcium-Calmodulin-Dependent Protein Kinases, Cell Cycle, Cell Line, Chromatin, DNA Helicases, DNA-Binding Proteins, Humans, Macromolecular Substances, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases, Mitosis, Nuclear Proteins, Nucleosomes, Phosphoprotein Phosphatases, Phosphorylation, Plasmids, Transcription Factors
Genes Dev.
Date: Sep. 15, 1998
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