4D genome conformation

  • Project leader:Philippe Collas
  • Info:The human genome is hierarchically organized in 3 dimensions, laying blueprints of developmental gene expression and cell homeostasis. Analysis of genome-wide 3D genome conformation (Hi-C) data has revealed, among other structures, topologically-associating domains (TADs), which constitute spatial units of gene regulation. The combination of Hi-C, lamin ChIP-seq data and restraint-based 3D genome modeling using our platform Chrom3D (Paulsen 2017 Genome Biol) has further led to the identification of long-range interactions between TADs forming TAD 'cliques', most of which form domains of inactive chromatin near the nuclear periphery (Paulsen 2019 Nat Genet). Other factors such as PML nuclear bodies and histone variants (e.g. histone H3.3) contribute to defining specific genomic domains (Delbarre 2013 Genome Res; Delbarre 2017 Genome Res). Our current examinations of chromatin organization in cell populations and at the single-cell level provide insights into the dynamics 3D genome conformation.

Project participants

Julia Madsen Østerbye, Aurélie Bellanger, Natalia Galigniana, Mohamed Abdelhalim, Kristin Vekterud, Anita Sørensen; collaborations with Jonas Paulsen (Institute of Biosciences, University of Oslo); Erwan Delbarre, Oslo Metropolitan University; David Tremethick, Australian National University, Canberra; Lee H. Wong, Monash University, Melbourne

Image: 3D model of chromatin in a human fibroblast nucleus. Model generated using Chrom3D , from Hi-C and lamin ChIP-seq data to infer chromosomal interactions and positioning of chromatin towards the nuclear periphery.

Ongoing research

  • Interplay between the nuclear lamina, LADs and TADs as genomic organizers in stem cells and cancer cells
  • Formation and disassembly of TAD cliques during differentiation
  • Nuclear lamins and EMT
  • Histone variant H3.3 and chromatin organization in pediatric glioblastomas
  • Computational methods for 3D genome modeling

Recent findings