A genome-wide relay of signalling-responsive enhancers drives hematopoietic specification

Benjamin Edginton-White*, A Maytum, S G Kellaway, D K Goode, P Keane, I Pagnuco, S A Assi, L Ames, M Clarke, P N Cockerill, B Göttgens, J B Cazier, C Bonifer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Developmental control of gene expression critically depends on distal cis-regulatory elements including enhancers which interact with promoters to activate gene expression. To date no global experiments have been conducted that identify their cell type and cell stage-specific activity within one developmental pathway and in a chromatin context. Here, we describe a high-throughput method that identifies thousands of differentially active cis-elements able to stimulate a minimal promoter at five stages of hematopoietic progenitor development from embryonic stem (ES) cells, which can be adapted to any ES cell derived cell type. We show that blood cell-specific gene expression is controlled by the concerted action of thousands of differentiation stage-specific sets of cis-elements which respond to cytokine signals terminating at signalling responsive transcription factors. Our work provides an important resource for studies of hematopoietic specification and highlights the mechanisms of how and where extrinsic signals program a cell type-specific chromatin landscape driving hematopoietic differentiation.

Original languageEnglish
Article number267
Number of pages20
JournalNature Communications
Volume14
Issue number1
DOIs
Publication statusPublished - 17 Jan 2023

Bibliographical note

© 2023. Crown.

Keywords

  • Regulatory Sequences, Nucleic Acid
  • Chromatin/genetics
  • Cell Differentiation/genetics
  • Transcription Factors/genetics
  • Promoter Regions, Genetic/genetics
  • Enhancer Elements, Genetic/genetics
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  • /49/109
  • Article
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  • /45/15
  • /631/337/572/2102
  • article
  • /38/91
  • /38
  • /49
  • /631/532/1542
  • /49/91
  • /631/136/142

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