Role of a DEF/Y motif in histone H2A-H2B recognition and nucleosome editing
| Autor: | Yan Huang, Lu Sun, Leonidas Pierrakeas, Linchang Dai, Lu Pan, Ed Luk, Zheng Zhou |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Saccharomyces cerevisiae Proteins animal structures Multidisciplinary Amino Acid Motifs Saccharomyces cerevisiae Biological Sciences Nucleosomes Histones 03 medical and health sciences 0302 clinical medicine embryonic structures 030217 neurology & neurosurgery Protein Binding Transcription Factors 030304 developmental biology |
| Zdroj: | Proc Natl Acad Sci U S A |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | The SWR complex edits the histone composition of nucleosomes at promoters to facilitate transcription by replacing the two nucleosomal H2A-H2B (A-B) dimers with H2A.Z-H2B (Z-B) dimers. Swc5, a subunit of SWR, binds to A-B dimers, but its role in the histone replacement reaction was unclear. In this study, we showed that Swc5 uses a tandem DEF/Y motif within an intrinsically disordered region to engage the A-B dimer. A 2.37-Å X-ray crystal structure of the histone binding domain of Swc5 in complex with an A-B dimer showed that consecutive acidic residues and flanking hydrophobic residues of Swc5 form a cap over the histones, excluding histone–DNA interaction. Mutations in Swc5 DEF/Y inhibited the nucleosome editing function of SWR in vitro. Swc5 DEF/Y interacts with histones in vivo, and the extent of this interaction is dependent on the remodeling ATPase of SWR, supporting a model in which Swc5 acts as a wedge to promote A-B dimer eviction. Given that DEF/Y motifs are found in other evolutionary unrelated chromatin regulators, this work provides the molecular basis for a general strategy used repeatedly during eukaryotic evolution to mobilize histones in various genomic functions. |
| Databáze: | OpenAIRE |
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