Chromatin remodeling factor encoded by ini1 induces G1 arrest and apoptosis in ini1-deficient cells - PubMed (original) (raw)

. 2002 May 9;21(20):3112-20.

doi: 10.1038/sj.onc.1205414.

Affiliations

Chromatin remodeling factor encoded by ini1 induces G1 arrest and apoptosis in ini1-deficient cells

Keisuke Ae et al. Oncogene. 2002.

Abstract

Ini1/hsnf5 gene encodes INI1 protein, a chromatin remodeling factor associated with the SWI/SNF complex. In yeast, this complex modifies chromatin condensation to coactivate various transcriptional factors. However, in human, little is known about the SWI/SNF complex and INI1. To elucidate cellular functions of ini1, we constructed a recombinant adenovirus (AdexHA-INI1) capable of overexpressing INI1 in ini1-deficient cells. AdexHA-INI1 produced intranuclear INI1 in three ini1-deficient cell lines, changed their morphology, and decreased the proportion of viable cells. Flow cytometry and a BrdU incorporation assay showed that after the infection, growth of these cells was partially arrested at G1. In two of the three ini1-deficient cell lines, apoptosis was found to occur after the infection, as detected by the presence of cleaved poly (ADP-ribose) polymerase. To determine functional domains of INI1, we constructed plasmids expressing INI1 and its deletion mutants, which were used for a colony formation assay. Repeats 1 and 2 of INI1 were found to be required to suppress the growth of the three ini1-deficient cell lines. The results support the hypothesis that ini1 is a tumor suppressor gene and suggest a novel link between human SWI/SNF chromatin remodeling complex and apoptosis.

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