| 项目编号 |
PRJCA016393 |
| 项目标题 |
Structural insights into the recognition of histone H3Q5 serotonylation by WDR5 |
| 涉及领域 |
Medical |
| 数据类型 |
Proteome
|
| 物种名称 |
Homo sapiens
|
| 描述信息 |
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. |
| 样品范围 |
protein structure |
| 发布日期 |
2025-02-23 |
| 出版信息 |
|
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| Chinese Academy of Sciences (CAS)
|
|
XDB37000000
|
|
|
|
| 提交者 |
Xuan
Zhang (xuanzbin@ustc.edu.cn)
|
| 提交单位 |
University of Science and Technology of China |
| 提交日期 |
2023-04-19 |
