Chromatin alternates between A and B compartments at kilobase scale for subgenic organization.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
06 06 2023
06 06 2023
Historique:
received:
02
02
2023
accepted:
28
04
2023
medline:
8
6
2023
pubmed:
7
6
2023
entrez:
6
6
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37280210
doi: 10.1038/s41467-023-38429-1
pii: 10.1038/s41467-023-38429-1
pmc: PMC10244318
doi:
Substances chimiques
Chromatin
0
CCCTC-Binding Factor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
3303Subventions
Organisme : NHGRI NIH HHS
ID : RM1 HG011016
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM067553
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG009375
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH115957
Pays : United States
Organisme : NIGMS NIH HHS
ID : R00 GM127671
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM147467
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM146852
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG009446
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM128645
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM139408
Pays : United States
Informations de copyright
© 2023. The Author(s).
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