During development, cellular identity is established by the complex interplay between transcriptional regulators, epigenetic factors and spatial proximity. Progress in defining genomic regulatory elements, such as enhancers, in tandem with a growing understanding of epigenetic processes has significantly illuminated the mechanisms that contribute to transcription regulation. However, important questions remain about how regulatory interactions are established in a temporal and tissue-specific manner to direct cell-fate decisions. Spatial organization of the genome has been shown to be dynamically altered during development, but to what extent these changes inform gene expression has remained unclear.
"We have comprehensively reviewed recent advances in understanding the causes and functional consequences of genome folding, emphasizing its multilayered nature, its importance for gene regulation and its spatiotemporal dynamics." - Erin Abelnour
Published on May 7th in Dev. Cell (DOI: 10.1016/j.devcel.2021.04.023), postdoctoral researcher Erin Aboelnour, together with her supervisor Boyan Bonev summarized recent advances in understanding the causes and functional consequences of genome folding, emphasizing its multilayered nature, its importance for gene regulation and its spatiotemporal dynamics. Evidence suggests that prominent 3D features, such as compartments and topologically associated domains (TADs) arise by distinct mechanisms during development, regulated by DNA sequence elements, architectural proteins and transcription factors. At local scales, regulatory contacts are similarly complex, with evidence for both pre-established and dynamic loops that are mediated by a variety of cis-acting factors and local chromatin structure.
Technical advances, including single-cell methods and live-cell imaging, are providing a new look at the heterogeneity and dynamics of chromatin folding, which suggests that the relationship between genomic contacts and molecular events like transcription are highly dynamic and stochastic. Application of these tools, as well as integration of multi-omics data will continue to develop our thinking of how spatial organization of the genome and gene expression intersects.
The research of the Bonev-lab at the Helmholtz Pioneer Campus is primarily funded by the Helmholtz Center Munich, a DFG priority program, and complimentary funds from the Helmholtz-Association.
Link to publication in Cell Press