Chromatin alternates between A and B compartments at kilobase scale for subgenic organization
Abstract Nuclear compartments are prominent features of 3D chromatin organization, but sequencing depth limitations have impeded investigation at ultra fine-scale. CTCF loops are generally studied at a finer scale, but the impact of looping on proximal interactions remains enigmatic. Here, we critic...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38429-1 |
| _version_ | 1797806629708627968 |
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| author | Hannah L. Harris Huiya Gu Moshe Olshansky Ailun Wang Irene Farabella Yossi Eliaz Achyuth Kalluchi Akshay Krishna Mozes Jacobs Gesine Cauer Melanie Pham Suhas S. P. Rao Olga Dudchenko Arina Omer Kiana Mohajeri Sungjae Kim Michael H. Nichols Eric S. Davis Dimos Gkountaroulis Devika Udupa Aviva Presser Aiden Victor G. Corces Douglas H. Phanstiel William Stafford Noble Guy Nir Michele Di Pierro Jeong-Sun Seo Michael E. Talkowski Erez Lieberman Aiden M. Jordan Rowley |
| author_facet | Hannah L. Harris Huiya Gu Moshe Olshansky Ailun Wang Irene Farabella Yossi Eliaz Achyuth Kalluchi Akshay Krishna Mozes Jacobs Gesine Cauer Melanie Pham Suhas S. P. Rao Olga Dudchenko Arina Omer Kiana Mohajeri Sungjae Kim Michael H. Nichols Eric S. Davis Dimos Gkountaroulis Devika Udupa Aviva Presser Aiden Victor G. Corces Douglas H. Phanstiel William Stafford Noble Guy Nir Michele Di Pierro Jeong-Sun Seo Michael E. Talkowski Erez Lieberman Aiden M. Jordan Rowley |
| author_sort | Hannah L. Harris |
| collection | DOAJ |
| description | Abstract Nuclear compartments are prominent features of 3D chromatin organization, but sequencing depth limitations have impeded investigation at ultra fine-scale. CTCF loops are generally studied at a finer scale, but the impact of looping on proximal interactions remains enigmatic. Here, we critically examine nuclear compartments and CTCF loop-proximal interactions using a combination of in situ Hi-C at unparalleled depth, algorithm development, and biophysical modeling. Producing a large Hi-C map with 33 billion contacts in conjunction with an algorithm for performing principal component analysis on sparse, super massive matrices (POSSUMM), we resolve compartments to 500 bp. Our results demonstrate that essentially all active promoters and distal enhancers localize in the A compartment, even when flanking sequences do not. Furthermore, we find that the TSS and TTS of paused genes are often segregated into separate compartments. We then identify diffuse interactions that radiate from CTCF loop anchors, which correlate with strong enhancer-promoter interactions and proximal transcription. We also find that these diffuse interactions depend on CTCF’s RNA binding domains. In this work, we demonstrate features of fine-scale chromatin organization consistent with a revised model in which compartments are more precise than commonly thought while CTCF loops are more protracted. |
| first_indexed | 2024-03-13T06:10:11Z |
| format | Article |
| id | doaj.art-273c83ceac55444f8d76b4044e6d0017 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T06:10:11Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-273c83ceac55444f8d76b4044e6d00172023-06-11T11:18:56ZengNature PortfolioNature Communications2041-17232023-06-0114111710.1038/s41467-023-38429-1Chromatin alternates between A and B compartments at kilobase scale for subgenic organizationHannah L. Harris0Huiya Gu1Moshe Olshansky2Ailun Wang3Irene Farabella4Yossi Eliaz5Achyuth Kalluchi6Akshay Krishna7Mozes Jacobs8Gesine Cauer9Melanie Pham10Suhas S. P. Rao11Olga Dudchenko12Arina Omer13Kiana Mohajeri14Sungjae Kim15Michael H. Nichols16Eric S. Davis17Dimos Gkountaroulis18Devika Udupa19Aviva Presser Aiden20Victor G. Corces21Douglas H. Phanstiel22William Stafford Noble23Guy Nir24Michele Di Pierro25Jeong-Sun Seo26Michael E. Talkowski27Erez Lieberman Aiden28M. Jordan Rowley29Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical CenterCenter for Genome Architecture, Department of Molecular and Human Genetics, Baylor College of MedicineComputational Biology and Clinical Informatics, Baker Heart and Diabetes InstituteCenter for Theoretical Biological Physics, Northeastern UniversityCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BISB)Center for Genome Architecture, Department of Molecular and Human Genetics, Baylor College of MedicineDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical CenterDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical CenterPaul G. Allen School of Computer Science & Engineering, University of WashingtonDepartment of Genome Sciences, University of WashingtonCenter for Genome Architecture, Department of Molecular and Human Genetics, Baylor College of MedicineCenter for Genome Architecture, Department of Molecular and Human Genetics, Baylor College of MedicineCenter for Genome Architecture, Department of Molecular and Human Genetics, Baylor College of MedicineCenter for Genome Architecture, Department of Molecular and Human Genetics, Baylor College of MedicineMassachusetts General HospitalMacrogen IncDepartment of Human Genetics, Emory University School of MedicineCurriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel HillCenter for Genome Architecture, Department of Molecular and Human Genetics, Baylor College of MedicineDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical CenterCenter for Genome Architecture, Department of Molecular and Human Genetics, Baylor College of MedicineDepartment of Human Genetics, Emory University School of MedicineCurriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel HillPaul G. Allen School of Computer Science & Engineering, University of WashingtonDepartment of Biochemistry and Molecular Biology, University of Texas Medical BranchCenter for Theoretical Biological Physics, Northeastern UniversityMacrogen IncMassachusetts General HospitalCenter for Genome Architecture, Department of Molecular and Human Genetics, Baylor College of MedicineDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical CenterAbstract Nuclear compartments are prominent features of 3D chromatin organization, but sequencing depth limitations have impeded investigation at ultra fine-scale. CTCF loops are generally studied at a finer scale, but the impact of looping on proximal interactions remains enigmatic. Here, we critically examine nuclear compartments and CTCF loop-proximal interactions using a combination of in situ Hi-C at unparalleled depth, algorithm development, and biophysical modeling. Producing a large Hi-C map with 33 billion contacts in conjunction with an algorithm for performing principal component analysis on sparse, super massive matrices (POSSUMM), we resolve compartments to 500 bp. Our results demonstrate that essentially all active promoters and distal enhancers localize in the A compartment, even when flanking sequences do not. Furthermore, we find that the TSS and TTS of paused genes are often segregated into separate compartments. We then identify diffuse interactions that radiate from CTCF loop anchors, which correlate with strong enhancer-promoter interactions and proximal transcription. We also find that these diffuse interactions depend on CTCF’s RNA binding domains. In this work, we demonstrate features of fine-scale chromatin organization consistent with a revised model in which compartments are more precise than commonly thought while CTCF loops are more protracted.https://doi.org/10.1038/s41467-023-38429-1 |
| spellingShingle | Hannah L. Harris Huiya Gu Moshe Olshansky Ailun Wang Irene Farabella Yossi Eliaz Achyuth Kalluchi Akshay Krishna Mozes Jacobs Gesine Cauer Melanie Pham Suhas S. P. Rao Olga Dudchenko Arina Omer Kiana Mohajeri Sungjae Kim Michael H. Nichols Eric S. Davis Dimos Gkountaroulis Devika Udupa Aviva Presser Aiden Victor G. Corces Douglas H. Phanstiel William Stafford Noble Guy Nir Michele Di Pierro Jeong-Sun Seo Michael E. Talkowski Erez Lieberman Aiden M. Jordan Rowley Chromatin alternates between A and B compartments at kilobase scale for subgenic organization Nature Communications |
| title | Chromatin alternates between A and B compartments at kilobase scale for subgenic organization |
| title_full | Chromatin alternates between A and B compartments at kilobase scale for subgenic organization |
| title_fullStr | Chromatin alternates between A and B compartments at kilobase scale for subgenic organization |
| title_full_unstemmed | Chromatin alternates between A and B compartments at kilobase scale for subgenic organization |
| title_short | Chromatin alternates between A and B compartments at kilobase scale for subgenic organization |
| title_sort | chromatin alternates between a and b compartments at kilobase scale for subgenic organization |
| url | https://doi.org/10.1038/s41467-023-38429-1 |
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