Dynamic and flexible bridging of H3K9me3-nucleosomes via HP1ß-dimerization establishes a plastic state of condensed chromatin

Histone H3 trimethylation of lysine 9 (H3K9me3) and heterochromatin proteins 1 (HP1) are hallmarks of heterochromatin, a state of compacted DNA essential for genome stability and long-term transcriptional silencing. The mechanisms by which H3K9me3 and HP1 contribute to chromatin compaction have been speculative and controversial. We demonstrate that mammalian HP1ß is a prototypic HP1 protein exemplifying most basal chromatin binding and effects. These are caused by dimeric and dynamic interaction with highly enriched H3K9me3 and are modulated by various electrostatic interfaces. Via internucleosomal bridging HP1ß specifically interacts with condensed chromatin, which we postulate stabilizes the compacted state. In agreement, HP1ß genome-wide localization follows enrichment of H3K9me3 and bridging of chromatin fibers in a cellular context is sufficient for maintaining heterochromatic conformation. Overall, our findings define a fundamental mechanism for chromatin higher order structural changes caused by HP1 proteins, which may contribute to the plastic nature of condensed chromatin. Overall design: HP1b ChIP-seq in mouse embryonic stem cells