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Sekiya T , Muthurajan UM , Luger K , Tulin AV , Zaret KS
Nucleosome-binding affinity as a primary determinant of the nuclear mobility of the pioneer transcription factor FoxA
Genes Dev. 2009 Apr 1;23(7) :804-9
PMID: 19339686    PMCID: PMC2666343   
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FoxA proteins are pioneer transcription factors, among the first to bind chromatin domains in development and enable gene activity. The Fox DNA-binding domain structurally resembles linker histone and binds nucleosomes stably. Using fluorescence recovery after photobleaching, we found that FoxA1 and FoxA2 move much more slowly in nuclei than other transcription factor types, including c-Myc, GATA-4, NF-1, and HMGB1. We find that slower nuclear mobility correlates with high nonspecific nucleosome binding, and point mutations that disrupt nonspecific binding markedly increase nuclear mobility. FoxA's distinct nuclear mobility is consistent with its pioneer activity in chromatin.
Sekiya, Takashi Muthurajan, Uma M Luger, Karolin Tulin, Alexei V Zaret, Kenneth S GM061909/GM/NIGMS NIH HHS/United States GM077452/GM/NIGMS NIH HHS/United States R01/R37GM36477/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Genes & development Genes Dev. 2009 Apr 1;23(7):804-9.