Cis-regulatory chromatin loops arise before TADs and gene activation, and are independent of cell fate during early Drosophila development.
IF: 41.307
Cited by: 84


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.


Spatial Genomics

MeSH terms

Cell Differentiation
Cell Lineage
Drosophila Proteins
Drosophila melanogaster
Embryo, Nonmammalian
Enhancer Elements, Genetic
Gene Expression Profiling
Gene Expression Regulation, Developmental
Nuclear Proteins
Promoter Regions, Genetic
Single-Cell Analysis
Transcription Factors
Transcription, Genetic


Espinola, Sergio Martin
Götz, Markus
Bellec, Maelle
Messina, Olivier
Fiche, Jean-Bernard
Houbron, Christophe
Dejean, Matthieu
Reim, Ingolf
Cardozo Gizzi, Andrés M
Lagha, Mounia
Nollmann, Marcelo

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