Selective interaction between the chromatin‐remodeling factor BRG1 and the heterochromatin‐associated protein HP1α

Mammalian heterochromatin protein 1 (HP1) α, HP1β and HP1γ are closely related non‐histone chromosomal proteins that function in gene silencing, presumably by organizing higher order chromatin structures. Here, we show by co‐immunoprecipitation that HP1α, but neither HP1β nor HP1γ, forms a complex with the BRG1 chromatin‐remodeling factor in HeLa cells. In vitro, BRG1 interacts directly and preferentially with HP1α. The region conferring this preferential binding has been mapped to residues 106–180 of the HP1α C‐terminal chromoshadow domain. Using site‐directed mutagenesis, we have identified three amino acid residues I113, A114 and C133 in HP1α (K, P and S in HP1β and HP1γ) that are essential for the selective interaction of HP1α with BRG1. Interestingly, these residues were also shown to be critical for the silencing activity of HP1α. Taken together, these results demonstrate that mammalian HP1 proteins are biochemically distinct and suggest an entirely novel function for BRG1 in modulating HP1α‐containing heterochromatic structures.

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