title: Histone H4 Facilitates the Proteolysis of the Budding Yeast CENP-ACse4 Centromeric Histone Variant.
abstract: The incorporation of histone variants into nucleosomes can alter chromatin-based processes. CENP-A is the histone H3 variant found exclusively at centromeres that serves as an epigenetic mark for centromere identity and is required for kinetochore assembly. CENP-A mislocalization to ectopic sites appears to contribute to genomic instability, transcriptional misregulation, and tumorigenesis, so mechanisms exist to ensure its exclusive localization to centromeres. One conserved process is proteolysis, which is mediated by the Psh1 E3 ubiquitin ligase in Saccharomyces cerevisiae (budding yeast). To determine whether there are features of the CENP-A nucleosome that facilitate proteolysis, we performed a genetic screen to identify histone H4 residues that regulate CENP-ACse4degradation. We found that H4-R36 is a key residue that promotes the interaction between CENP-ACse4and Psh1 Consistent with this, CENP-ACse4protein levels are stabilized in H4-R36A mutant cells and CENP-ACse4is enriched in the euchromatin. We propose that the defects in CENP-ACse4proteolysis may be related to changes in Psh1 localization, as Psh1 becomes enriched at some 3' intergenic regions in H4-R36A mutant cells. Together, these data reveal a key residue in histone H4 that is important for efficient CENP-ACse4degradation, likely by facilitating the interaction between Psh1 and CENP-ACse4.
authors: Howard Hughes Medical Institute, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98040.|Department of Health Services Research, University of Texas MD Anderson Cancer Center, Houston, Texas 77030.
authors: Gary M R
authors: GM
authors: Deyter
authors: Howard Hughes Medical Institute, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98040.|Molecular and Cellular Biology Program, University of Washington, Seattle, Washington 98195.
authors: Erica M
authors: EM
authors: Hildebrand
authors: Howard Hughes Medical Institute, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98040.
authors: Adrienne D
authors: AD
authors: Barber
authors: Howard Hughes Medical Institute, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98040 sbiggins@fredhutch.org.
authors: Sue
authors: 0000-0002-4499-6319
authors: S
authors: Biggins
mesh_terms: D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D002503:Centromere / Q000378:metabolism*; D000076247:Centromere Protein A; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D022041:Euchromatin; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D011485:Protein Binding; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D054875:Ubiquitination
chemical_list: D001324:Autoantigens; D000076247:Centromere Protein A; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D022041:Euchromatin; D006657:Histones; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D044767:Ubiquitin-Protein Ligases
keywords: CENP-ACse4; H4; Psh1; centromere; nucleosome; proteolysis