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Interaction of HP1 and Brg1/Brm with the Globular Domain of Histone H3 Is Required for HP1-Mediated Repression
11.12.2009
The heterochromatin-enriched HP1 proteins play a critical role in regulation of transcription. These proteins contain two
related domains known as the chromo- and the chromoshadow-domain. The chromo-domain binds histone H3 tails
methylated on lysine 9. However, in vivo and in vitro experiments have shown that the affinity of HP1 proteins to native
methylated chromatin is relatively poor and that the opening of chromatin occurring during DNA replication facilitates their
binding to nucleosomes. These observations prompted us to investigate whether HP1 proteins have additional histone
binding activities, envisioning also affinity for regions potentially occluded by the nucleosome structure. We find that the
chromoshadow-domain interacts with histone H3 in a region located partially inside the nucleosomal barrel at the entry/exit
point of the nucleosome. Interestingly, this region is also contacted by the catalytic subunits of the human SWI/SNF
complex. In vitro, efficient SWI/SNF remodeling requires this contact and is inhibited in the presence of HP1 proteins. The
antagonism between SWI/SNF and HP1 proteins is also observed in vivo on a series of interferon-regulated genes. Finally,
we show that SWI/SNF activity favors loading of HP1 proteins to chromatin both in vivo and in vitro. Altogether, our data
suggest that HP1 chromoshadow-domains can benefit from the opening of nucleosomal structures to bind chromatin and
that HP1 proteins use this property to detect and arrest unwanted chromatin remodeling.
