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The Sir4 H‐ BRCT domain interacts with phospho‐proteins to sequester and repress yeast heterochromatin
Author(s) -
Deshpande Ishan,
Keusch Jeremy J,
Challa Kiran,
Iesmantavicius Vytautas,
Gasser Susan M,
Gut Heinz
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019101744
Subject(s) - biology , heterochromatin , yeast , saccharomyces cerevisiae , dna binding protein , microbiology and biotechnology , genetics , plasma protein binding , chromatin , gene , transcription factor
Abstract In Saccharomyces cerevisiae , the silent information regulator ( SIR ) proteins Sir2/3/4 form a complex that suppresses transcription in subtelomeric regions and at the homothallic mating‐type ( HM ) loci. Here, we identify a non‐canonical BRCA 1 C‐terminal domain (H‐ BRCT ) in Sir4, which is responsible for tethering telomeres to the nuclear periphery. We show that Sir4 H‐ BRCT and the closely related Dbf4 H‐ BRCT serve as selective phospho‐epitope recognition domains that bind to a variety of phosphorylated target peptides. We present detailed structural information about the binding mode of established Sir4 interactors (Esc1, Ty5, Ubp10) and identify several novel interactors of Sir4 H‐ BRCT , including the E3 ubiquitin ligase Tom1. Based on these findings, we propose a phospho‐peptide consensus motif for interaction with Sir4 H‐ BRCT and Dbf4 H‐ BRCT . Ablation of the Sir4 H‐ BRCT phospho‐peptide interaction disrupts SIR ‐mediated repression and perinuclear localization. In conclusion, the Sir4 H‐ BRCT domain serves as a hub for recruitment of phosphorylated target proteins to heterochromatin to properly regulate silencing and nuclear order.