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. 2021 Apr;53(4):477-486.
doi: 10.1038/s41588-021-00816-z. Epub 2021 Apr 1.

Cis-regulatory chromatin loops arise before TADs and gene activation, and are independent of cell fate during early Drosophila development

Sergio Martin Espinola #  1 , Markus Götz #  1 , Maelle Bellec  2 , Olivier Messina  1   2 , Jean-Bernard Fiche  1 , Christophe Houbron  1 , Matthieu Dejean  2 , Ingolf Reim  3 , Andrés M Cardozo Gizzi  4 , Mounia Lagha  5 , Marcelo Nollmann  6
Affiliations

Cis-regulatory chromatin loops arise before TADs and gene activation, and are independent of cell fate during early Drosophila development

Sergio Martin Espinola et al. Nat Genet. 2021 Apr.

Abstract

Acquisition of cell fate is thought to rely on the specific interaction of remote cis-regulatory modules (CRMs), for example, enhancers and target promoters. However, the precise interplay between chromatin structure and gene expression is still unclear, particularly within multicellular developing organisms. In the present study, we employ Hi-M, a single-cell spatial genomics approach, to detect CRM-promoter looping interactions within topologically associating domains (TADs) during early Drosophila development. By comparing cis-regulatory loops in alternate cell types, we show that physical proximity does not necessarily instruct transcriptional states. Moreover, multi-way analyses reveal that multiple CRMs spatially coalesce to form hubs. Loops and CRM hubs are established early during development, before the emergence of TADs. Moreover, CRM hubs are formed, in part, via the action of the pioneer transcription factor Zelda and precede transcriptional activation. Our approach provides insight into the role of CRM-promoter interactions in defining transcriptional states, as well as distinct cell types.

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