8VLD
Crystal structure of Ash1L PHD finger in complex with histone H3K4me2
Summary for 8VLD
| Entry DOI | 10.2210/pdb8vld/pdb |
| Descriptor | Histone-lysine N-methyltransferase ASH1L, Histone H3.3C, ZINC ION, ... (4 entities in total) |
| Functional Keywords | ash1l, h3k4me2, zinc finger, transcriptional regulation, transferase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 15759.57 |
| Authors | |
| Primary citation | Vann, K.R.,Sharma, R.,Hsu, C.C.,Devoucoux, M.,Tencer, A.H.,Zeng, L.,Lin, K.,Zhu, L.,Li, Q.,Lachance, C.,Ospina, R.R.,Tong, Q.,Cheung, K.L.,Yang, S.,Biswas, S.,Xuan, H.,Gatchalian, J.,Alamillo, L.,Wang, J.,Jang, S.M.,Klein, B.J.,Lu, Y.,Ernst, P.,Strahl, B.D.,Rothbart, S.B.,Walsh, M.J.,Cleary, M.L.,Cote, J.,Shi, X.,Zhou, M.M.,Kutateladze, T.G. Structure-function relationship of ASH1L and histone H3K36 and H3K4 methylation. Nat Commun, 16:2235-2235, 2025 Cited by PubMed Abstract: The histone H3K36-specific methyltransferase ASH1L plays a critical role in development and is frequently dysregulated in human diseases, particularly cancer. Here, we report on the biological functions of the C-terminal region of ASH1L encompassing a bromodomain (ASH1L), a plant homeodomain (ASH1L) finger, and a bromo-adjacent homology (ASH1L) domain, structurally characterize these domains, describe their mechanisms of action, and explore functional crosstalk between them. We find that ASH1L recognizes H3K4me2/3, whereas the neighboring ASH1L and ASH1L have DNA binding activities. The DNA binding function of ASH1L is a driving force for the association of ASH1L with the linker DNA in the nucleosome, and the large interface with ASH1L stabilizes the ASH1L fold, merging two domains into a single module. We show that ASH1L is involved in embryonic stem cell differentiation and co-localizes with H3K4me3 but not with H3K36me2 at transcription start sites of target genes and genome wide, and that the interaction of ASH1L with H3K4me3 is inhibitory to the H3K36me2-specific catalytic activity of ASH1L. Our findings shed light on the mechanistic details by which the C-terminal domains of ASH1L associate with chromatin and regulate the enzymatic function of ASH1L. PubMed: 40044670DOI: 10.1038/s41467-025-57556-5 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.92 Å) |
Structure validation
Download full validation report
