Dynamic Control of Enhancer Repertoires Drives Lineage and Stage-Specific Transcription during Hematopoiesis

Jialiang Huang, Xin Liu, Dan Li, Zhen Shao, Hui Cao, Yuannyu Zhang, Eirini Trompouki, Teresa V. Bowman, Leonard I. Zon, Guo Cheng Yuan, Stuart H. Orkin, Jian Xu

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Enhancers are the primary determinants of cell identity, but the regulatory components controlling enhancer turnover during lineage commitment remain largely unknown. Here we compare the enhancer landscape, transcriptional factor occupancy, and transcriptomic changes in human fetal and adult hematopoietic stem/progenitor cells and committed erythroid progenitors. We find that enhancers are modulated pervasively and direct lineage- and stage-specific transcription. GATA2-to-GATA1 switch is prevalent at dynamic enhancers and drives erythroid enhancer commissioning. Examination of lineage-specific enhancers identifies transcription factors and their combinatorial patterns in enhancer turnover. Importantly, by CRISPR/Cas9-mediated genomic editing, we uncover functional hierarchy of constituent enhancers within the SLC25A37 super-enhancer. Despite indistinguishable chromatin features, we reveal through genomic editing the functional diversity of several GATA switch enhancers in which enhancers with opposing functions cooperate to coordinate transcription. Thus, genome-wide enhancer profiling coupled with in situ enhancer editing provide critical insights into the functional complexity of enhancers during development.

Original languageEnglish (US)
Pages (from-to)9-23
Number of pages15
JournalDevelopmental cell
Volume36
Issue number1
DOIs
StatePublished - Jan 11 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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    Huang, J., Liu, X., Li, D., Shao, Z., Cao, H., Zhang, Y., Trompouki, E., Bowman, T. V., Zon, L. I., Yuan, G. C., Orkin, S. H., & Xu, J. (2016). Dynamic Control of Enhancer Repertoires Drives Lineage and Stage-Specific Transcription during Hematopoiesis. Developmental cell, 36(1), 9-23. https://doi.org/10.1016/j.devcel.2015.12.014