MITOTIC INACTIVATION OF A HUMAN SWI SNF CHROMATIN REMODELING COMPLEX/

During mitosis, chromatin is condensed into mitotic chromosomes and tr anscription is inhibited, processes that might be opposed by the chrom atin remodeling activity of the SWI/SNF complexes. Brg1 and hBrm, whic h are components of human SWI/SNF (hSWIISNF) complexes, were recently shown to be phosphorylated during mitosis. This suggested that phospho rylation might be used as a switch to modulate SWI/SNF activity. Using an epitope-tag strategy, we have purified hSWI/SNF complexes at diffe rent stages of the cell cycle, and found that hSWI/SNF was inactive in cells blocked in G(2)-M. Mitotic hSWI/SNF contained Brg1 but trot hBr m, 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/SN F isolated as cells traversed mitosis regained activity when its subun its were dephosphorylated either in vitro or in vivo. We propose that this transitional inactivation and reactivation of hSWI/SNF is require d for formation of a repressed chromatin structure during mitosis and reformation of an active chromatin structure as cells leave mitosis.