PXD047651-2

PXD047651 is an original dataset announced via ProteomeXchange.

Title	Identification of a novel, tunable interface in the S.pombe HP1 protein, Swi6, that underpins epigenetic inheritance.
Description	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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:54:03.897.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Amanda Ames
SpeciesList	scientific name: Schizosaccharomyces pombe; NCBI TaxID: 4896;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-08 07:38:57	ID requested
1	2024-08-10 12:01:58	announced
⏵ 2	2024-10-22 06:54:07	announced	2024-10-22: Updated project metadata.

10.1038/s41467-024-50538-z;

Ames A, Seman M, Larkin A, Raiymbek G, Chen Z, Levashkevich A, Kim B, Biteen JS, Ragunathan K, Epigenetic memory is governed by an effector recruitment specificity toggle in Heterochromatin Protein 1. Nat Commun, 15(1):6276(2024) [pubmed]

submitter keyword: TMT-MS, epigenetics, QuantIP

Kaushik Ragunathan
contact affiliation	Department of Biology, Brandeis University
contact email	kaushikr@brandeis.edu
lab head
Amanda Ames
contact affiliation	Brandeis University
contact email	amandaames@brandeis.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/08/PXD047651

PRIDE project URI

• PRIDE
  1. PXD047651
     1. Label: PRIDE project
     2. Name: Identification of a novel, tunable interface in the S.pombe HP1 protein, Swi6, that underpins epigenetic inheritance.