Chromatin conformation, gene transcription, and nucleosome remodeling as an emergent system
DownloadLuay M Almassalha 1 2, Marcelo Carignano 2 3, Emily Pujadas Liwag 2 4, Wing Shun Li 2 3 5, Ruyi Gong 2 3, Nicolas Acosta 2 3, Cody L Dunton 2 3, Paola Carrillo Gonzalez 2 3, Lucas M Carter 2 4, Rivaan Kakkaramadam 2 4, Martin Kröger 6, Kyle L MacQuarrie 7 8, Jane Frederick 2 3, I Chae Ye 2 3, Patrick Su 2 3, Tiffany Kuo 2 4, Karla I Medina 2 4, Josh A Pritchard 2 3, Andrew Skol 7, Rikkert Nap 2 3, Masato Kanemaki 9 10 11, Vinayak Dravid 5 12 13 14 15, Igal Szleifer 2 3 12, Vadim Backman 2 3
DOI: https://doi.org/10.1126/sciadv.adq6652
Abstract: In single cells, variably sized nanoscale chromatin structures are observed, but it is unknown whether these form a cohesive framework that regulates RNA transcription. Here, we demonstrate that the human genome is an emergent, self-assembling, reinforcement learning system. Conformationally defined heterogeneous, nanoscopic packing domains form by the interplay of transcription, nucleosome remodeling, and loop extrusion. We show that packing domains are not topologically associated domains. Instead, packing domains exist across a structure-function life cycle that couples heterochromatin and transcription in situ, explaining how heterochromatin enzyme inhibition can produce a paradoxical decrease in transcription by destabilizing domain cores. Applied to development and aging, we show the pairing of heterochromatin and transcription at myogenic genes that could be disrupted by nuclear swelling. In sum, packing domains represent a foundation to explore the interactions of chromatin and transcription at the single-cell level in human health.
- AlphaFold Links exist in Table S1: https://www.science.org/doi/suppl/10.1126/sciadv.adq6652/suppl_file/sciadv.adq6652_sm.pdf
- Public ChIP-seq data from ENCODE used in Figure 5 exists in Table S2: https://www.science.org/doi/suppl/10.1126/sciadv.adq6652/suppl_file/sciadv.adq6652_sm.pdf
DOI: None
Zenodo URL: None
Created at: 24th Apr 2025 at 18:12
Cell Culture - Metadata
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P.BAC-250422-V1_CellCulture_ChromatinConformation.docx
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- CellCulture_ChromatinConformation.docx
Cell Imaging - Data Linked
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P.BAC-250422-V1_ChromatinElectronMicroscopy_ChromatinConformation.docx
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- ChromatinElectronMicroscopy_ChromatinConformation.docx
P.BAC-250422-V1_PWS_ChromatinConformation.docx
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- PWS_ChromatinConformation.docx
P.BAC-250422-V1_SMLM_ChromatinConformation.docx
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- SMLM_ChromatinConformation.docx
Imaging Analysis - Data Linked
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P.BAC-250422-V1_ChromatinElectronMicroscopy_ChromatinConformation.docx
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- ChromatinElectronMicroscopy_ChromatinConformation.docx
P.BAC-250422-V1_PWS_ChromatinConformation.docx
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- PWS_ChromatinConformation.docx
P.BAC-250422-V1_SMLM_ChromatinConformation.docx
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- SMLM_ChromatinConformation.docx
Library Creation - Metadata
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P.BAC-250422-V1_Hi-C_ChromatinConformation.docx
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- Hi-C_ChromatinConformation.docx
Short Read Sequencing - Data Linked
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P.BAC-250422-V1_Hi-C_ChromatinConformation.docx
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- Hi-C_ChromatinConformation.docx
Chromatin Sequencing Analysis - Data Linked
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P.BAC-250422-V1_Hi-C_ChromatinConformation.docx
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- Hi-C_ChromatinConformation.docx
Modeling - Data Linked
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P.BAC-250424-V1_Modeling_ChromatinConformation.pdf
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- Modeling_ChromatinConformation.pdf
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Created: 24th Apr 2025 at 18:12
