Pioneer transcription factors shape the epigenetic landscape

Pioneer transcription factors have the unique and important role of unmasking chromatin domains during development to allow the implementation of new cellular programs. Compared with those of other transcription factors, this activity implies that pioneer factors can recognize their target DNA sequences in so-called compacted or “closed” heterochromatin and can trigger remodeling of the adjoining chromatin landscape to provide accessibility to nonpioneer transcription factors. Recent studies identified several steps of pioneer action, namely rapid but weak initial binding to heterochromatin and stabilization of binding followed by chromatin opening and loss of cytosine-phosphate-guanine (CpG) methylation that provides epigenetic memory. Whereas CpG demethylation depends on replication, chromatin opening does not. In this Minireview, we highlight the unique properties of this transcription factor class and the challenges of understanding their mechanism of action.

• Publication year

  2018

• Venue

  Journal of Biological Chemistry

• Publication date

  2018-03-05

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.R117.001232PMID 29507097PMCID PMC6130937
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Genetic determinants and epigenetic effects of pioneer factor occupancy

  2018influential reference
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  2018influential reference
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