Integrative analysis of transcriptomic and epigenomic data reveals distinct patterns for developmental and housekeeping gene regulation

Irina Abnizova, Carine Stapel, Rene te Boekhorst, Jimmy Tsz Hang Lee, Martin Hemberg

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Regulation of transcription is central to the emergence of new cell types during development, and it often involves activation of genes via proximal and distal regulatory regions. The activity of regulatory elements is determined by transcription factors (TFs) and epigenetic marks, but despite extensive mapping of such patterns, the extraction of regulatory principles remains challenging. Results: Here we study differentially and similarly expressed genes along with their associated epigenomic profiles, chromatin accessibility and DNA methylation, during lineage specification at gastrulation in mice. Comparison of the three lineages allows us to identify genomic and epigenomic features that distinguish the two classes of genes. We show that differentially expressed genes are primarily regulated by distal elements, while similarly expressed genes are controlled by proximal housekeeping regulatory programs. Differentially expressed genes are relatively isolated within topologically associated domains, while similarly expressed genes tend to be located in gene clusters. Transcription of differentially expressed genes is associated with differentially open chromatin at distal elements including enhancers, while that of similarly expressed genes is associated with ubiquitously accessible chromatin at promoters. Conclusion: Based on these associations of (linearly) distal genes’ transcription start sites (TSSs) and putative enhancers for developmental genes, our findings allow us to link putative enhancers to their target promoters and to infer lineage-specific repertoires of putative driver transcription factors, within which we define subgroups of pioneers and co-operators.
Original languageEnglish
Article number78
Pages (from-to)1-20
Number of pages20
JournalBMC Biology
Volume22
Issue number1
Early online date10 Apr 2024
DOIs
Publication statusPublished - 10 Apr 2024

Keywords

  • Transcriptional architecture
  • Epigenomics
  • Pioneer TFs
  • Gene regulation programs
  • Developmental and housekeeping genes
  • Differentially and similarly expressed genes
  • Animals
  • Chromatin/genetics
  • Gene Expression Profiling
  • Mice
  • Transcription Factors/genetics
  • Genes, Essential

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