Low input capture Hi-C (liCHi-C) identifies promoter-enhancer interactions at high-resolution.
Por:
Tomás-Daza L, Rovirosa L, López-Martí P, Nieto-Aliseda A, Serra F, Planas-Riverola A, Molina O, McDonald R, Ghevaert C, Cuatrecasas E, Costa D, Camós-Guijosa M, Bueno C, Menéndez P, Valencia A and Javierre BM
Publicada:
17 ene 2023
Ahead of Print:
17 ene 2023
Resumen:
Long-range interactions between regulatory elements and promoters are key in gene transcriptional control; however, their study requires large amounts of starting material, which is not compatible with clinical scenarios nor the study of rare cell populations. Here we introduce low input capture Hi-C (liCHi-C) as a cost-effective, flexible method to map and robustly compare promoter interactomes at high resolution. As proof of its broad applicability, we implement liCHi-C to study normal and malignant human hematopoietic hierarchy in clinical samples. We demonstrate that the dynamic promoter architecture identifies developmental trajectories and orchestrates transcriptional transitions during cell-state commitment. Moreover, liCHi-C enables the identification of disease-relevant cell types, genes and pathways potentially deregulated by non-coding alterations at distal regulatory elements. Finally, we show that liCHi-C can be harnessed to uncover genome-wide structural variants, resolve their breakpoints and infer their pathogenic effects. Collectively, our optimized liCHi-C method expands the study of 3D chromatin organization to unique, low-abundance cell populations, and offers an opportunity to uncover factors and regulatory networks involved in disease pathogenesis.
Filiaciones:
Tomás-Daza L:
Josep Carreras Leukaemia Research Institute, Badalona, Barcelona, Spain
Barcelona Supercomputing Center, Barcelona, Barcelona, Spain
Rovirosa L:
Josep Carreras Leukaemia Research Institute, Badalona, Barcelona, Spain
López-Martí P:
Josep Carreras Leukaemia Research Institute, Badalona, Barcelona, Spain
Barcelona Supercomputing Center, Barcelona, Barcelona, Spain
Nieto-Aliseda A:
Josep Carreras Leukaemia Research Institute, Badalona, Barcelona, Spain
Serra F:
Josep Carreras Leukaemia Research Institute, Badalona, Barcelona, Spain
Planas-Riverola A:
Josep Carreras Leukaemia Research Institute, Badalona, Barcelona, Spain
Molina O:
Josep Carreras Leukaemia Research Institute, Badalona, Barcelona, Spain
McDonald R:
Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK
Ghevaert C:
Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK
NHS Blood and Transplant, Cambridge, UK
Cuatrecasas E:
Pediatric Institute of Rare Diseases, Sant Joan de Déu Hospital, Esplugues de Llobregat, Barcelona, Spain
Costa D:
Hospital Clinic, Barcelona, Spain
Institute of Biomedical Research August Pi i Sunyer, Barcelona, Spain
Cancer Network Biomedical Research Center, Barcelona, Spain
Camós-Guijosa M:
Sant Joan de Déu Research Institute, Esplugues de Llobregat, Barcelona, Spain
Sant Joan de Déu Hospital, Esplugues de Llobregat, Barcelona, Spain
Center for Biomedical Research in the Rare Diseases Network (CIBERER), Carlos III Health Institute, Madrid, Spain
Bueno C:
Josep Carreras Leukaemia Research Institute, Badalona, Barcelona, Spain
Menéndez P:
Josep Carreras Leukaemia Research Institute, Badalona, Barcelona, Spain
Catalan Institution for research and Advanced Studies (ICREA), Barcelona, Spain
Valencia A:
Barcelona Supercomputing Center, Barcelona, Barcelona, Spain
Catalan Institution for research and Advanced Studies (ICREA), Barcelona, Spain
Javierre BM:
Josep Carreras Leukaemia Research Institute, Badalona, Barcelona, Spain.
Institute for Health Science Research Germans Trias i Pujol, Badalona, Barcelona, Spain.
Green Submitted, gold
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