Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Sep 7;293(36):13795-13804.
doi: 10.1074/jbc.R117.001232. Epub 2018 Mar 5.

Pioneer transcription factors shape the epigenetic landscape

Alexandre Mayran  1 , Jacques Drouin  2
Affiliations
Review

Pioneer transcription factors shape the epigenetic landscape

Alexandre Mayran et al. J Biol Chem. .

Abstract

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.

Keywords: DNA demethylation; cell differentiation; chromatin remodeling; development; epigenetics; gene transcription.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflicts of interest with the contents of this article

Figures

Figure 1.
Figure 1.
Salient properties of pioneer factors.
Figure 2.
Figure 2.
Current scheme of pioneer action. The permissive chromatin state for pioneer action appears to be facultative heterochromatin. Following initial weak binding of the pioneer, target site chromatin (mostly characterized at enhancers) undergoes a first transition where a central nucleosome becomes more accessible, and this may (or not) overlap with a state of Primed enhancer characterized by a weak H3K4me1 signal. Complete activation of enhancers is characterized by nucleosome depletion, bimodal distribution of H3K4me1 and H3K27ac, together with recruitment of the general coactivator p300 and other transcription factors. Whereas the ability to bind methylated DNA target sites is not a unique feature of all pioneers, for most pioneers the current evidence correlates pioneer-dependent chromatin remodeling with loss of CpG methylation at the newly accessible DNA/enhancers.
See this image and copyright information in PMC

References

    1. Garcia-Bellido A. (1975) Genetic control of wing disc development in Drosophila. Ciba Found. Symp. 0, 161–182 - PubMed
    1. Hobert O. (2008) Regulatory logic of neuronal diversity: terminal selector genes and selector motifs. Proc. Natl. Acad. Sci. U.S.A. 105, 20067–20071 10.1073/pnas.0806070105 - DOI - PMC - PubMed
    1. Cirillo L. A., and Zaret K. S. (1999) An early developmental transcription factor complex that is more stable on nucleosome core particles than on free DNA. Mol. Cell 4, 961–969 10.1016/S1097-2765(00)80225-7 - DOI - PubMed
    1. Sérandour A. A., Avner S., Percevault F., Demay F., Bizot M., Lucchetti-Miganeh C., Barloy-Hubler F., Brown M., Lupien M., Métivier R., Salbert G., and Eeckhoute J. (2011) Epigenetic switch involved in activation of pioneer factor FOXA1-dependent enhancers. Genome Res. 21, 555–565 10.1101/gr.111534.110 - DOI - PMC - PubMed
    1. Gardner K. E., Allis C. D., and Strahl B. D. (2011) Operating on chromatin, a colorful language where context matters. J. Mol. Biol. 409, 36–46 10.1016/j.jmb.2011.01.040 - DOI - PMC - PubMed