Topologically associated domains enriched for lineagespecific genes reveal expression-dependent nuclear topologies during myogenesis

Daniel S. Neems, Arturo G. Garza-Gongora, Erica D. Smith, Steven T. Kosak*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


The linear distribution of genes across chromosomes and the spatial localization of genes within the nucleus are related to their transcriptional regulation. The mechanistic consequences of linear gene order, and how it may relate to the functional output of genome organization, remain to be fully resolved, however. Here we tested the relationship between linear and 3D organization of gene regulation during myogenesis. Our analysis has identified a subset of topologically associated domains (TADs) that are significantly enriched for muscle-specific genes. These lineage-enriched TADs demonstrate an expression-dependent pattern of nuclear organization that influences the positioning of adjacent nonenriched TADs. Therefore, lineageenriched TADs inform cell-specific genome organization during myogenesis. The reduction of allelic spatial distance of one of these domains, which contains Myogenin, correlates with reduced transcriptional variability, identifying a potential role for lineage-specific nuclear topology. Using a fusion-based strategy to decouple mitosis and myotube formation, we demonstrate that the cell-specific topology of syncytial nuclei is dependent on cell division. We propose that the effects of linear and spatial organization of gene loci on gene regulation are linked through TAD architecture, and that mitosis is critical for establishing nuclear topologies during cellular differentiation.

Original languageEnglish (US)
Pages (from-to)E1691-E1700
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number12
StatePublished - Mar 22 2016


  • 3D image analysis
  • Cell differentiation
  • Gene regulation
  • Nuclear organization
  • Transcriptional noise

ASJC Scopus subject areas

  • General

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