Spatial Genome Architecture in Development & Disease

Welcome to our DFG-funded priority program

The Programme

Features of mammalian genome organization (from Robson et al, Mol Cell 2019)
Super-resolution imaging of CTCF (red) and cohesin (green) distribution (from Zhang et al, Sci Adv 2021)
Chrom3D model of the human genome (from Sofiadis et al, Mol Syst Biol 2021)
GAM vs Hi-C data from mESCs (from Beagrie et al, Nature 2017)

Programme Description

Eukaryotic genomes encode the information that defines both general and specific characteristics of each cell type. However, the linear DNA sequence alone often fails to predict cellular functions and phenotypic outcomes. In fact, genomic information is modified and regulated by a number of additional layers of gene expression control. One of these, the spatial folding of chromosomes, has been recently identified as a critical such layer. Spatial chromosomal folding is established through binding of transcription factors as well as via epigenetic mechanisms and biophysical forces that act in a concerted manner to regulate gene expression in space and time. Therefore, studying the principles of three-dimensional chromatin folding allow us to unravel its contribution in gene regulation during development and disease. This Priority Program, SPP2202, began its work in 2019 and has brought together >30 Principal and Affiliated Investigators from different sites across Germany to promote this emerging research area.

Major Aims

In our effort to further the emerging field of spatial genome organization, SPP2202 researchers work to meet the following major aims:

  • To develop and apply novel technologies that can capture spatial chromatin conformation, also in conjunction with other genomic features (e.g., transcription, histone modifications, DNA methylation), to resolve and track features of genomic architecture in the nucleus down to the single cell-level
  • to functionally dissect the impact of 3D chromatin folding on gene expression using in vitro and in vivo model systems or human samples during cell differentiation
  • To causally connect 3D chromatin folding with disease pathology by integrating precision genome editing and patient data and/or disease models
  • To develop and apply novel computational approaches that will allow us to integrate, visualise, and quantitatively model the end-effects and dynamics of spatial genome organisation

By focusing on chromatin folding and gene regulation, the SPP2202 consortium addresses a field of biomedicine that goes beyond the study of genes and their function in order to fully understand their regulation. Building on one of the most important discoveries in Genomics of the past decade, we take the next step in investigating how chromatin folding governs differentiation, development, and disease, thereby addressing a pertinent question in Life Sciences: how cellular individuality is achieved at a genomic level. Once deciphered, these rules will allow us to predict how different cell types respond to signaling cues upon development or disease manifestation.

Funded since 2019

Program Committee

  • Papantonis, Argyris

    Göttingen

  • Furlong, Eileen

    Heidelberg

  • Pombo, Ana

    Berlin

  • Mundlos, Stefan

    Berlin

Phase II Projects

Affiliate Projects