Pioneer transcription factors: establishing competence for gene expression.

By K. Zaret, Jason S. Carroll. Genes & Development, 2011

1,584 citations recorded by the source corpus.

Transcription factors are adaptor molecules that detect regulatory sequences in the DNA and target the assembly of protein complexes that control gene expression. Yet much of the DNA in the eukaryotic cell is in nucleosomes and thereby occluded by histones, and can be further occluded by higher-order chromatin structures and repressor complexes. Indeed, genome-wide location analyses have revealed that, for all transcription factors tested, the vast majority of potential DNA-binding sites are unoccupied, demonstrating the inaccessibility of most of the nuclear DNA. This raises the question of how target sites at silent genes become bound de novo by transcription factors, thereby initiating regulatory events in chromatin. Binding cooperativity can be sufficient for many kinds of factors to simultaneously engage a target site in chromatin and activate gene expression. However, in cases in which the binding of a series of factors is sequential in time and thus not initially cooperative, special "pioneer transcription factors" can be the first to engage target sites in chromatin. Such initial binding can passively enhance transcription by reducing the number of additional factors that are needed to bind the DNA, culminating in activation. In addition, pioneer factor binding can actively open up the local chromatin and directly make it competent for other factors to bind. Passive and active roles for the pioneer factor FoxA occur in embryonic development, steroid hormone induction, and human cancers. Herein we review the field and describe how pioneer factors may enable cellular reprogramming.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f9d723b94bcaa230978b0c3de2e657ed1c636702

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Citations in the corpus

Transcription factor binding in human cells occurs in dense clusters formed around cohesin anchor sites. (2013, positive): “Recovery of individual clusters that would fail to retain cohesin across the cell cycle, and establishment of new TF clusters in turn would occur via loading of cohesin by pioneer TFs (Zaret and Carroll, 2011).”
Modification of enhancer chromatin: what, how and why? (2013, background): “For example, various acetylation marks, including H3K9ac and H3K18ac, were detected at putative enhancers (Ernst et al., 2011; Zentner et al., 2011), as was histone crotonylation (Tan et al., 2011), H3K79me2/3 (Bonn et al., 2012; Djebali et al., 2012), and, in the context of poised enhancers, H3K9me”
Pioneer Transcription Factors Target Partial DNA Motifs on Nucleosomes to Initiate Reprogramming (2015, positive): “However, a select group of transcription factors (TFs) known as pioneer factors have the combined ability to access their target sites in silent chromatin and initiate cell-fate changes (Iwafuchi-Doi and Zaret, 2014; Zaret and Carroll, 2011).”
Systematic discovery and characterization of regulatory motifs in ENCODE TF binding experiments (2013, background): “Conversely, FOXA has a DNA binding domain and plays an important role in liver development and function (70) and is a pioneer factor responsible for priming chromatin for the binding of other factors (reviewed in (71)].”
Facilitators and Impediments of the Pluripotency Reprogramming Factors’ Initial Engagement with the Genome (2012, positive): “…factors on their own could extensively engage DNaseI-resistant chromatin lacking detectable histone marks and that the factors could permit c-Myc to gain access to its target sites where c-Myc could not do so on its own; these are all features expected of pioneer factors (Zaret and Carroll, 2011).”
The Sox Family of Transcription Factors: Versatile Regulators of Stem and Progenitor Cell Fate (2013, positive): “Sox Proteins as Pioneer Factors Pioneer factors are transcription factors that occupy silenced target genes in progenitor cells and keep them in a poised state for activation at subsequent stages of differentiation (Zaret and Carroll, 2011).”
Ever-changing landscapes: transcriptional enhancers in development and evolution (2016, background): “These factors can recruit chromatin remodeling activities, which then facilitate removal and post-translational modification of histones, meaning that subsequent TF and coactivator binding is less strictly dependent on direct competition between TFs and nucleosomes (Zaret and Carroll, 2011).”
Gene regulatory network inference in the era of single-cell multi-omics (2023, background): “Changes in DNA accessibility can be triggered by the binding of so-called pioneer TFs 2 .”
Establishment of regions of genomic activity during the Drosophila maternal to zygotic transition (2014, background): “Nature of chromatin changes during MZT During the first stage of embryonic development, the genome must be reprogrammed from the differentiated states associated with the egg or sperm to create a set of totipotent cells capable of generating a new organism.”