| Accession |
PRJCA016393 |
| Title |
Structural insights into the recognition of histone H3Q5 serotonylation by WDR5 |
| Relevance |
Medical |
| Data types |
Protein complex structure
|
| Organisms |
Homo sapiens
|
| Description |
Serotonylation of histone H3Q5 (H3Q5ser) is a recently identified posttranslational modification of histones that acts as a permissive marker for gene activation in synergy with H3K4me3 during neuronal cell differentiation. However, any proteins that specifically recognize H3Q5ser remain unknown. Here, we found that WDR5 interacts with the N-terminal tail of histone H3 and functions as a "reader" for H3Q5ser. Crystal structures of WDR5 in complex with H3Q5ser and H3K4me3Q5ser peptides revealed that the serotonyl group is accommodated in a shallow surface pocket of WDR5. Experiments in neuroblastoma cells demonstrate that H3K4me3 modification is hampered upon disruption of WDR5-H3Q5ser interaction. WDR5 colocalizes with H3Q5ser in the promoter regions of cancer-promoting genes in neuroblastoma cells, where it promotes gene transcription to induce cell proliferation. Thus, beyond revealing a previously unknown mechanism through which WDR5 reads H3Q5ser to activate transcription, our study suggests that this WDR5-H3Q5ser-mediated epigenetic regulation apparently promotes tumorigenesis. |
| Sample scope |
Synthetic |
| Release date |
2024-04-19 |
| Publication |
| PubMed ID |
Article title |
Journal name |
DOI |
Year |
| 34144982
|
|
|
|
|
|
|
| Grants |
| Agency |
program |
Grant ID |
Grant title |
| Chinese Academy of Sciences (CAS)
|
|
XDB37010105
|
|
|
|
| Submitter |
Xuan
Zhang (xuanzbin@ustc.edu.cn)
|
| Organization |
University of Science and Technology of China |
| Submission date |
2023-04-19 |
