8G87
Human Oct4 bound to nucleosome with human nMatn1 sequence (focused refinement of Oct4 bound region)
Summary for 8G87
| Entry DOI | 10.2210/pdb8g87/pdb |
| Related | 8G86 8G88 8G8B 8G8E 8G8G |
| EMDB information | 29837 29841 29843 29845 29846 29850 |
| Descriptor | nMatn1 DNA (top strand), nMatn1 DNA (bottom strand), POU domain, class 5, transcription factor 1 (3 entities in total) |
| Functional Keywords | oct4, nucleosome, pioneer factor, nmatn1 dna, dna binding protein-dna complex, dna binding protein/dna |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 157122.90 |
| Authors | Sinha, K.K.,Bilokapic, S.,Du, Y.,Malik, D.,Halic, M. (deposition date: 2023-02-17, release date: 2023-03-22, Last modification date: 2024-06-19) |
| Primary citation | Sinha, K.K.,Bilokapic, S.,Du, Y.,Malik, D.,Halic, M. Histone modifications regulate pioneer transcription factor cooperativity. Nature, 619:378-384, 2023 Cited by PubMed Abstract: Pioneer transcription factors have the ability to access DNA in compacted chromatin. Multiple transcription factors can bind together to a regulatory element in a cooperative way, and cooperation between the pioneer transcription factors OCT4 (also known as POU5F1) and SOX2 is important for pluripotency and reprogramming. However, the molecular mechanisms by which pioneer transcription factors function and cooperate on chromatin remain unclear. Here we present cryo-electron microscopy structures of human OCT4 bound to a nucleosome containing human LIN28B or nMATN1 DNA sequences, both of which bear multiple binding sites for OCT4. Our structural and biochemistry data reveal that binding of OCT4 induces changes to the nucleosome structure, repositions the nucleosomal DNA and facilitates cooperative binding of additional OCT4 and of SOX2 to their internal binding sites. The flexible activation domain of OCT4 contacts the N-terminal tail of histone H4, altering its conformation and thus promoting chromatin decompaction. Moreover, the DNA-binding domain of OCT4 engages with the N-terminal tail of histone H3, and post-translational modifications at H3K27 modulate DNA positioning and affect transcription factor cooperativity. Thus, our findings suggest that the epigenetic landscape could regulate OCT4 activity to ensure proper cell programming. PubMed: 37225990DOI: 10.1038/s41586-023-06112-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (8.1 Å) |
Structure validation
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