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Cryo-EM structure of the S. cerevisiae chromatin remodeler Yta7 hexamer bound to ADP
Structural highlights
FunctionATAD2_YEAST Functions as an ATP-dependent nucleosome disassembly factor that helps evict canonical histone H3 from the 5'-end of genes upon their induction (PubMed:25406467). Also contributes to kinetochore assembly by cooperating with SCM3 to load the histone H3 variant CSE4/CENP-A at centromeres (PubMed:32079723). Provides a chromatin boundary function at the 5'-end of genes that restricts access by RTT106 and thus prevents ectopic spreading of repressive chromatin into coding regions (PubMed:19683497, PubMed:22156209, PubMed:25406467). Also prevents heterochromatin spreading downstream of the silent mating-type locus HMR, this function is independent of the tRNA boundary element (PubMed:16079223). Contributes to appropriate cell cycle regulation of histone gene expression by recruiting RNA polymerase II to histone genes, and subsequent CDK1- and casein kinase II-dependent eviction from chromatin is required to promote transcriptional elongation (PubMed:22156209).[1] [2] [3] [4] [5] Publication Abstract from PubMedThe Saccharomyces cerevisiae Yta7 is a chromatin remodeler harboring a histone-interacting bromodomain (BRD) and two AAA+ modules. It is not well understood how Yta7 recognizes the histone H3 tail to promote nucleosome disassembly for DNA replication or RNA transcription. By cryo-EM analysis, here we show that Yta7 assembles a three-tiered hexamer with a top BRD tier, a middle AAA1 tier, and a bottom AAA2 tier. Unexpectedly, the Yta7 BRD stabilizes a four-stranded beta-helix, termed BRD-interacting motif (BIM), of the largely disordered N-terminal region. The BIM motif is unique to the baker's yeast, and we show both BRD and BIM contribute to nucleosome recognition. We found that Yta7 binds both acetylated and nonacetylated H3 peptides but with a higher affinity for the unmodified peptide. This property is consistent with the absence of key residues of canonical BRDs involved in acetylated peptide recognition and the role of Yta7 in general nucleosome remodeling. Interestingly, the BRD tier exists in a spiral and a flat-ring form on top of the Yta7 AAA+ hexamer. The spiral is likely in a nucleosome-searching mode because the bottom BRD blocks the entry to the AAA+ chamber. The flat ring may be in a nucleosome disassembly state because the entry is unblocked and the H3 peptide has entered the AAA+ chamber and is stabilized by the AAA1 pore loops 1 and 2. Indeed, we show that the BRD tier is a flat ring when bound to the nucleosome. Overall, our study sheds light on the nucleosome disassembly by Yta7. The Saccharomyces cerevisiae Yta7 ATPase hexamer contains a unique bromodomain tier that functions in nucleosome disassembly.,Wang F, Feng X, He Q, Li H, Li H J Biol Chem. 2023 Feb;299(2):102852. doi: 10.1016/j.jbc.2022.102852. Epub 2022 , Dec 30. PMID:36592926[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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