Enhancer-dependence of gene expression increases with developmental age

Wenqing Cai, Jialiang Huang, Qian Zhu, Bin E. Li, Davide Seruggia, Pingzhu Zhou, Minh Nguyen, Yuko Fujiwara, Huafeng Xie, Zhenggang Yang, Danni Hong, Pengfei Ren, Jian Xu, William T. Pu, Guo Cheng Yuan, Stuart H. Orkin

Research output: Contribution to journalArticlepeer-review

Abstract

How overall principles of gene regulation (the "logic") may change during ontogeny is largely unexplored. We compared transcriptomic, epigenomic and topological profiles in embryonic (EryP) and adult (EryD) erythroblasts. Despite reduced chromatin accessibility compared to EryP, distal chromatin of EryD is enriched in H3K27ac, Gata1 and Myb occupancy. In contrast to EryP-specific genes, which exhibit promoter-centric regulation through Gata1, EryD-specific genes employ distal enhancers for long-range regulation through enhancer-promoter looping, confirmed by Gata1 HiChIP. Genome editing demonstrated distal enhancers are required for gene expression in EryD but not in EryP. Applying a metric for enhancer-dependence of transcription, we observed a progressive reliance on enhancer control with increasing age of ontogeny among diverse primary cells and tissues of mouse and human origin. Our findings highlight fundamental and conserved differences in regulatory logic at distinct developmental stages, characterized by simpler promoter-centric regulation in embryonic cells and combinatorial enhancer-driven control in adult cells.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Jun 21 2019

Keywords

  • Active enhancer
  • Enhancer dependent-regulatory logic
  • Enhancer-promoter interactions
  • Erythropoiesis
  • Gata1
  • HiChIP
  • Myb

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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