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.[1] Pioneer factors are involved in initiating cell differentiation and activation of cell-specific genes. This property is observed in histone fold-domain containing transcription factors (fork head box (FOX)[2] and NF-Y[3]) and other transcription factors that use zinc finger(s) for DNA binding (Groucho TLE, Gal4, and GATA).[2][4]
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.
^Cirillo LA, Lin FR, Cuesta I, Friedman D, Jarnik M, Zaret KS (February 2002). "Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4". Molecular Cell. 9 (2): 279–89. doi:10.1016/S1097-2765(02)00459-8. PMID 11864602.
^ abZaret, Kenneth S.; Carroll, Jason S. (2011-11-01). "Pioneer transcription factors: establishing competence for gene expression". Genes & Development. 25 (21): 2227–2241. doi:10.1101/gad.176826.111. ISSN 1549-5477. PMC 3219227. PMID 22056668.
^Oldfield, Andrew J.; Yang, Pengyi; Conway, Amanda E.; Cinghu, Senthilkumar; Freudenberg, Johannes M.; Yellaboina, Sailu; Jothi, Raja (2014-09-04). "Histone-fold domain protein NF-Y promotes chromatin accessibility for cell type-specific master transcription factors". Molecular Cell. 55 (5): 708–722. doi:10.1016/j.molcel.2014.07.005. ISSN 1097-4164. PMC 4157648. PMID 25132174.
^Magnani L, Eeckhoute J, Lupien M (November 2011). "Pioneer factors: directing transcriptional regulators within the chromatin environment". Trends in Genetics. 27 (11): 465–74. doi:10.1016/j.tig.2011.07.002. PMID 21885149.
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