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1000
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Abstract/Summary
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Binding of heterochromatin protein 1 (HP1) to the histone H3 lysine 9 trimethylation (H3K9me3) mark is a hallmark of establishment and maintenance of heterochromatin. Although genetic and cell biological aspects have been elucidated, the molecular details of HP1 binding to H3K9me3 nucleosomes are unknown. Using a combination of NMR spectroscopy and biophysical measurements on fully defined recombinant experimental systems, we demonstrate that H3K9me3 works as an on/off switch regulating distinct binding modes of hHP1β to the nucleosome. The methyl-mark determines a highly flexible and very dynamic interaction of the chromodomain of hHP1β with the H3-tail. There are no other constraints of interaction or additional multimerization interfaces. In contrast, in the absence of methylation, the hinge region and the N-terminal tail form weak nucleosome contacts mainly with DNA. In agreement with the high flexibility within the hHP1β-H3K9me3 nucleosome complex, the chromoshadow domain does not provide a direct binding interface. Our results report the first detailed structural analysis of a dynamic protein-nucleosome complex directed by a histone modification and provide a conceptual framework for understanding similar interactions in the context of chromatin.
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CAPSULE:
BACKGROUND: Chromatin-HP1 (heterochromatin protein 1) interaction is crucial for heterochromatin assembly.
RESULTS: hHP1β uses alternative interfaces to bind nucleosomes depending on histone 3 methylation within a highly dynamic complex.
CONCLUSION: hHP1β explores chromatin for sites of methyl-mark enrichment where it can bind histone 3 tails from adjacent nucleosomes.
SIGNIFICANCE: We provide a conceptual framework to understand the molecular basis of dynamic interactions regulated by histone modification.
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