Abstract

Unlike most transcription factors (TF), pioneer TFs have a specialized role in binding closed regions of chromatin and initiating the subsequent opening of these regions. Thus, pioneer TFs are key factors in gene regulation with critical roles in developmental transitions, including organ biogenesis, tissue development, and cellular differentiation. These developmental events involve some major reprogramming of gene expression patterns, specifically the opening and closing of distinct chromatin regions. Here, we discuss how pioneer TFs are identified using biochemical and genome-wide techniques. What is known about pioneer TFs from animals and plants is reviewed, with a focus on the strategies used by pioneer factors in different organisms. Finally, the different molecular mechanisms pioneer factors used are discussed, highlighting the roles that tertiary and quaternary structures play in nucleosome-compatible DNA-binding.

Highlights

  • Transcription factors (TFs) are DNA-binding proteins that read genomic information to control gene expression in all organisms [1,2,3,4,5]

  • Histone proteins can compete with TFs for DNA-binding, limiting access to transcription factor binding sites (TFBS) [9]

  • Eukaryotes have evolved a unique set of TFs that are able to bind to their cognate motifs even when nucleosomes are present, subsequently priming the region for access by other DNA-interacting or modifying proteins

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Summary

Introduction

Transcription factors (TFs) are DNA-binding proteins that read genomic information to control gene expression in all organisms [1,2,3,4,5]. Histone proteins can compete with TFs for DNA-binding, limiting access to transcription factor binding sites (TFBS) [9] This chromatin barrier poses a significant challenge to the establishment of new gene regulatory networks, which is required, for example, during developmental phase transitions or organ specification. To overcome such obstacles, eukaryotes have evolved a unique set of TFs that are able to bind to their cognate motifs even when nucleosomes are present, subsequently priming the region for access by other DNA-interacting or modifying proteins. TFs pioneer bind and Additional reviews of pioneer focusing on different different aspects of their activity, can elsewhere be found elsewhere forinformation further information onkey these key players aspects of their activity, can be found for further on these players in gene in gene regulation regulation [14,15,16,17,18,19,20,21,22]. [14,15,16,17,18,19,20,21,22]

Activity ofof pioneer factorsbind bindnucleosomal nucleosomalDNA
Identification ofof
ChIP-Seq and Variants
Chromatin Accessibility Assays
Chromosome Conformation Capture Assays
A Cautionary Note
Mammalian Models
Plant Pioneer Factors
Mechanism of Action
Pioneer Factors Recruit Chromatin Remodelers
Pioneer Factor Binding and Methylation of DNA and Histones
Pioneer Factors Impact the Epigenetic Landscape
Perspectives and Challenges
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