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 UdupaAviva 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

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish (US)
Article number3303
JournalNature communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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