Proteomics

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Identification of a novel, tunable interface in the S.pombe HP1 protein, Swi6, that underpins epigenetic inheritance.


ABSTRACT: HP1 proteins bind dynamically to H3K9 methylation and are essential for establishing and maintaining transcriptionally silent epigenetic states, known as heterochromatin. HP1 proteins can dimerize, forming a binding interface that interacts with and recruits diverse chromatin-associated factors. HP1 proteins rapidly evolve through sequence changes and gene duplications, but the extent of variation required to achieve functional specialization is unknown. To investigate how changes in amino acid sequence impact epigenetic inheritance, we performed a targeted mutagenesis screen of the dimerization and protein interaction domain of the S.pombe HP1 homolog Swi6. We discovered that substitutions mapping to an auxiliary motif in Swi6 outside the dimerization interface can lead to complete functional divergence. Specifically, we identified point mutations at a single amino acid residue that resulted in either persistent gain or loss of function in epigenetic inheritance without affecting heterochromatin establishment. These substitutions increase Swi6 chromatin occupancy in vivo and alter Swi6-protein interactions that selectively affect H3K9me inheritance. Based on our findings, we propose that relatively minor changes in Swi6 amino acid composition can lead to profound changes in epigenetic inheritance, underscoring the remarkable plasticity associated with HP1 proteins and their ability to evolve new functions.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Schizosaccharomyces Pombe

SUBMITTER: Amanda Ames  

LAB HEAD: Kaushik Ragunathan

PROVIDER: PXD047651 | Pride | 2024-08-10

REPOSITORIES: Pride

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Publications

Epigenetic memory is governed by an effector recruitment specificity toggle in Heterochromatin Protein 1.

Ames Amanda A   Seman Melissa M   Larkin Ajay A   Raiymbek Gulzhan G   Chen Ziyuan Z   Levashkevich Alex A   Kim Bokyung B   Biteen Julie Suzanne JS   Ragunathan Kaushik K  

Nature communications 20240725 1


HP1 proteins are essential for establishing and maintaining transcriptionally silent heterochromatin. They dimerize, forming a binding interface to recruit diverse chromatin-associated factors. Although HP1 proteins are known to rapidly evolve, the extent of variation required to achieve functional specialization is unknown. To investigate how changes in amino acid sequence impacts heterochromatin formation, we performed a targeted mutagenesis screen of the S. pombe HP1 homolog, Swi6. Substituti  ...[more]

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