Pioneering the developmental frontier

Mol Cell. 2021 Apr 15;81(8):1640-1650. doi: 10.1016/j.molcel.2021.02.020. Epub 2021 Mar 8.


Coordinated changes in gene expression allow a single fertilized oocyte to develop into a complex multi-cellular organism. These changes in expression are controlled by transcription factors that gain access to discrete cis-regulatory elements in the genome, allowing them to activate gene expression. Although nucleosomes present barriers to transcription factor occupancy, pioneer transcription factors have unique properties that allow them to bind DNA in the context of nucleosomes, define cis-regulatory elements, and facilitate the subsequent binding of additional factors that determine gene expression. In this capacity, pioneer factors act at the top of gene-regulatory networks to control developmental transitions. Developmental context also influences pioneer factor binding and activity. Here we discuss the interplay between pioneer factors and development, their role in driving developmental transitions, and the influence of the cellular environment on pioneer factor binding and activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • DNA / genetics
  • Gene Expression Regulation, Developmental / genetics*
  • Gene Regulatory Networks / genetics*
  • Genome / genetics
  • Humans
  • Nucleosomes / genetics
  • Protein Binding / genetics
  • Regulatory Elements, Transcriptional / genetics
  • Transcription Factors / genetics


  • Nucleosomes
  • Transcription Factors
  • DNA