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Recognition of modification status on a histone H3 tail by linked histone reader modules of the epigenetic regulator UHRF1.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Arita, Kyohei Isogai, Shin Oda, Takashi Unoki, Motoko Sugita, Kazuya Sekiyama, Naotaka Kuwata, Keiko Hamamoto, Ryuji Tochio, Hidehito Sato, Mamoru Ariyoshi, Mariko Shirakawa, Masahiro |
| Copyright Year | 2012 |
| Abstract | Multiple covalent modifications on a histone tail are often recognized by linked histone reader modules. UHRF1 [ubiquitin-like, containing plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1], an essential factor for maintenance of DNA methylation, contains linked two-histone reader modules, a tandem Tudor domain and a PHD finger, tethered by a 17-aa linker, and has been implicated to link histone modifications and DNA methylation. Here, we present the crystal structure of the linked histone reader modules of UHRF1 in complex with the amino-terminal tail of histone H3. Our structural and biochemical data provide the basis for combinatorial readout of unmodified Arg-2 (H3-R2) and methylated Lys-9 (H3-K9) by the tandem tudor domain and the PHD finger. The structure reveals that the intermodule linker plays an essential role in the formation of a histone H3-binding hole between the reader modules by making extended contacts with the tandem tudor domain. The histone H3 tail fits into the hole by adopting a compact fold harboring a central helix, which allows both of the reader modules to simultaneously recognize the modification states at H3-R2 and H3-K9. Our data also suggest that phosphorylation of a linker residue can modulate the relative position of the reader modules, thereby altering the histone H3-binding mode. This finding implies that the linker region plays a role as a functional switch of UHRF1 involved in multiple regulatory pathways such as maintenance of DNA methylation and transcriptional repression. |
| File Format | PDF HTM / HTML |
| DOI | 10.1073/pnas.1203701109 |
| PubMed reference number | 22837395 |
| Journal | Medline |
| Volume Number | 109 |
| Issue Number | 32 |
| Alternate Webpage(s) | http://www.pnas.org/content/109/32/12950.full.pdf?with-ds=yes |
| Alternate Webpage(s) | https://doi.org/10.1073/pnas.1203701109 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
