| Accession | GMS-83-2
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| Title | In silico nanoscope to study the interplay of genome organization and transcription regulation |
| Submit date | 2025-03-20 11:24:42 |
| Last update date | 2025-03-20 18:07:59 |
| Contact | Shoji TAKADA takada AT biophys.kyoto-u.ac.jp Kyoto University |
| Sharing | |
| Total file size | 2.54 GB |
| Keywords | Nanog gene Transcription factor RNA polymerase II Chromatin Nanoscale |
| Experiment type | Computational modeling based on experimental data including Micro-C, ChIP-seq, chemical mapping of nucleosome positioning, and cryo EM. |
| Summary | We develop a multiscale modeling pipeline to build near-atomistic models of the 200 kb Nanog gene locus in mouse embryonic stem cells comprising nucleosomes, transcription factors, co-activators, and RNA polymerase II-Mediator complexes. By integrating diverse experimental data, including protein localization, genomic interaction frequencies, cryo-electron microscopy, and single-molecule fluorescence studies, our model offers novel insights into chromatin organization and its role in enhancer-promoter communication. The models equilibrated by high-performance molecular dynamics simulations span a scale of ~350 nm, revealing an experimentally consistent local and global organization of chromatin and transcriptional machinery. Our models elucidate that the sequence-regulated chromatin accessibility facilitates the recruitment of transcription regulatory proteins exclusively at CREs, guided by the contrasting nucleosome organization compared to other regions. |
| Citation(s) | Soundhararajan Gopi, Giovanni B Brandani, Cheng Tan, Jaewoon Jung, Chenyang Gu, Azuki Mizutani, Hiroshi Ochiai, Yuji Sugita, and Shoji Takada (2025) In silico nanoscope to study the interplay of genome organization and transcription regulation, Nuc. Acids Res. |
| Organism | Mouse |
| Cell (Tissue) | embryonic stem cell |
| Protocol | The genome contact frequencies are used to build a 1kb-resolution polymer structural ensemble of 3D chromatin conformations using Hi-C metainference method (Brandani, PNAS Nexus 2024). Based on chemical mapping and ChIP-seq experimental data, we employ data-driven Monte Carlo simulations to generate an ensemble representation of nucleosome positioning and protein localization consistent with the experiments. The representative protein positional maps and 1kb-resolution chromatin conformation are combined using a backmapping pipeline to generate the molecular model of the Nanog locus at near-atomistic resolution. |
| Data processing | Structure models of 5 cluster centers equilibrated by short MD simulations are deposited with cif, pse (PYMOL), and gro (GENESIS) files. The system contains DNA (grey), core histones (pink), linker histones (orange), BRD4 (purple), SOX2 (green), OCT4 (green), NANOG (green), KLF4 (green), P300 (yellow), and Pol II/Mediator complex (black). In addition, illustrative movie files and a readme file are contained. |
| [689] Eq_Struct_Cluster1.cif
Cluster 1 application/octet-stream 262.66 MB MD5: 67dfc89109696ce71707fa4adc9e666e |
| [686] Eq_Struct_Cluster2.cif
Cluster 2 application/octet-stream 262.66 MB MD5: 67dfc89109696ce71707fa4adc9e666e |
| [687] Eq_Struct_Cluster3.cif
Cluster 3 application/octet-stream 262.66 MB MD5: 67dfc89109696ce71707fa4adc9e666e |
| [688] Eq_Struct_Cluster4.cif
Cluster 4 application/octet-stream 262.66 MB MD5: 67dfc89109696ce71707fa4adc9e666e |
| [690] Eq_Struct_Cluster5.cif
Cluster 5 application/octet-stream 262.66 MB MD5: 67dfc89109696ce71707fa4adc9e666e |
| [675] Struct_Cluster1-5.zip
ZIP (Cif, Gro, Pse) application/x-zip-compressed 1.07 GB MD5: a33b2472b3d32b6decd7e503a0664b2b |
| [674] READ_ME.txt
ReadMe.txt text/plain 1.74 KB MD5: 6e62a992c676f611616097dbea8ea030 |
| [681] Eq_Cluster1_rock.mp4
Cluster 1 video/mp4 25.16 MB MD5: e2386546a239fddf2e874da6eb0865f9 |
| [678] Eq_Cluster1_zoomin.mp4
Cluster 1 video/mp4 5.45 MB MD5: 7615c4886e8f724978eb2ea452bd1daf |
| [683] Eq_Cluster2_rock.mp4
Cluster 2 video/mp4 38.23 MB MD5: f818d8672fb3de31d41a301cafe30e39 |
| [680] Eq_Cluster3_rock.mp4
Cluster 3 video/mp4 33.76 MB MD5: fb41eb6da1e08f2efad4cb4236b08ae3 |
| [682] Eq_Cluster4_rock.mp4
Cluster 4 video/mp4 34.44 MB MD5: dea61fbfae0e58073f28ddd97fecadce |
| [679] Eq_Cluster5_rock.mp4
Cluster 5 video/mp4 16.92 MB MD5: f71cbec9a48e740b89a8e43021b3f7fe |
