Pioneer factor

Pioneer factors are transcription factors that can directly bind condensed chromatin. They can have positive and negative effects on transcription and are important in recruiting other transcription factors and histone modification enzymes as well as controlling DNA methylation. They were first discovered in 2002 as factors capable of binding to target sites on nucleosomal DNA in compacted chromatin and endowing competency for gene activity during hepatogenesis. Pioneer factors are involved in initiating cell differentiation and activation of cell-specific genes. This property is observed in fork head box (FOX), Groucho TEL, and in Gal4 transcription factors.

The eukaryotic cell condenses its genome into tightly packed chromatin and nucleosomes. This ability saves space in the nucleus for only actively transcribed genes and hides unnecessary or detrimental genes from being transcribed. Access to these condensed regions is done by chromatin remodelling by either balancing histone modifications or directly with pioneer factors that can loosen the chromatin themselves or as a flag recruiting other factors. Pioneer factors are not necessarily required for assembly of the transcription apparatus and may dissociate after being replaced by other factors.

Pioneer factors can also actively affect transcription by directly opening up condensed chromatin in an ATP-independent process. This is a common trait of fork head factors as they contain a winged helix DNA-binding domain that mimics the DNA-binding domain of the linker H1 histone. The similarity to histone H1 explains how it is able to bind chromatin by interacting with the major groove of only the one available side of DNA wrapped around a nucleosome. Fork head domains also have a helix that confers sequence specificity unlike linker histone. The C terminus is associated with higher mobility around the nucleosome than linker histone, displacing it and rearranging nucleosomal landscapes effectively. This active re-arrangement of the nucleosomes allows for other transcription factors to bind the available DNA. In thyroid cell differentiation FoxE binds to compacted chromatin of the thyroid peroxidase promoter and opens it for NF1 binding.

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