Chromatin Architecture Emerges during Zygotic Genome Activation Independent of Transcription

Cell. 2017 Apr 6;169(2):216-228.e19. doi: 10.1016/j.cell.2017.03.024.


Chromatin architecture is fundamental in regulating gene expression. To investigate when spatial genome organization is first established during development, we examined chromatin conformation during Drosophila embryogenesis and observed the emergence of chromatin architecture within a tight time window that coincides with the onset of transcription activation in the zygote. Prior to zygotic genome activation, the genome is mostly unstructured. Early expressed genes serve as nucleation sites for topologically associating domain (TAD) boundaries. Activation of gene expression coincides with the establishment of TADs throughout the genome and co-localization of housekeeping gene clusters, which remain stable in subsequent stages of development. However, the appearance of TAD boundaries is independent of transcription and requires the transcription factor Zelda for locus-specific TAD boundary insulation. These results offer insight into when spatial organization of the genome emerges and identify a key factor that helps trigger this architecture.

Keywords: Drosophila melanogaster; RNA polymerase II; TAD; Zelda; chromatin conformation; embryonic development; maternal to zygotic transition; topologically associating domains; transcription activation; zygotic genome activation.

MeSH terms

  • Animals
  • Chromatin / metabolism*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics*
  • Embryo, Nonmammalian / metabolism
  • Genes, Essential
  • Genome, Insect*
  • Nuclear Proteins
  • RNA Polymerase II / metabolism
  • Time Factors
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transcriptional Activation*
  • Zygote / metabolism*


  • Chromatin
  • Drosophila Proteins
  • Nuclear Proteins
  • Transcription Factors
  • zld protein, Drosophila
  • RNA Polymerase II