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Histone mutations that suppress the silencing defects caused by a yeast sir3 Ala2Gly mutation
Author(s) -
Sternglanz Rolf,
Wang Xiaorong,
Sampath Vinaya
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a467-e
Subject(s) - gene silencing , genetics , biology , histone h3 , histone , nucleosome , mutation , histone h4 , gene , microbiology and biotechnology
Transcriptional silencing in S. cerevisiae is mediated by the binding of a Sir3‐Sir4 complex to the N‐terminal regions of histones H4 and H3 after their deacetylation by Sir2. The known histone binding domain of Sir3 occurs in the C‐terminal third of the protein. The extreme N‐terminus of Sir3 is also important for its silencing function but the binding partner(s) of this region of Sir3 are not known. In order to learn more about the function of the Sir3 N‐terminus, we have carried out a screen to identify suppressors of the silencing defect of a sir3 Ala2Gly mutation. Two dominant suppressor mutations were found to be in the genes for histones H3 and H4. One changed H3 Asp77 to Asn and the other changed H4 His75 to Tyr. Both these residues are in a region of the nucleosome where mutations are known that affect silencing both positively and negatively. This region is very near Lys79, the residue methylated by Dot1, and whose modification is known to affect silencing. The possibility that the very N‐terminus of Sir3 binds to this region of the nucleosome is being explored. Two recessive suppressor mutations, not in the genes for H3 and H4, were also identified in this screen, and are currently being characterized.