Chromatin alternates between A and B compartments at kilobase scale for subgenic organization

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 Pierro, Jeong-Sun Seo, Michael E. Talkowski, Erez Lieberman Aiden () and M. Jordan Rowley ()
Additional contact information
Hannah L. Harris: University of Nebraska Medical Center
Huiya Gu: Baylor College of Medicine
Moshe Olshansky: Baker Heart and Diabetes Institute
Ailun Wang: Northeastern University
Irene Farabella: Barcelona Institute of Science and Technology (BISB)
Yossi Eliaz: Baylor College of Medicine
Achyuth Kalluchi: University of Nebraska Medical Center
Akshay Krishna: University of Nebraska Medical Center
Mozes Jacobs: University of Washington
Gesine Cauer: University of Washington
Melanie Pham: Baylor College of Medicine
Suhas S. P. Rao: Baylor College of Medicine
Olga Dudchenko: Baylor College of Medicine
Arina Omer: Baylor College of Medicine
Kiana Mohajeri: Massachusetts General Hospital
Sungjae Kim: Macrogen Inc
Michael H. Nichols: Emory University School of Medicine
Eric S. Davis: University of North Carolina at Chapel Hill
Dimos Gkountaroulis: Baylor College of Medicine
Devika Udupa: University of Nebraska Medical Center
Aviva Presser Aiden: Baylor College of Medicine
Victor G. Corces: Emory University School of Medicine
Douglas H. Phanstiel: University of North Carolina at Chapel Hill
William Stafford Noble: University of Washington
Guy Nir: University of Texas Medical Branch
Michele Pierro: Northeastern University
Jeong-Sun Seo: Macrogen Inc
Michael E. Talkowski: Massachusetts General Hospital
Erez Lieberman Aiden: Baylor College of Medicine
M. Jordan Rowley: University of Nebraska Medical Center

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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Citations: View citations in EconPapers (3)

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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38429-1

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DOI: 10.1038/s41467-023-38429-1

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