Nucleosome-binding affinity as a primary determinant of the nuclear mobility of the pioneer transcription factor FoxA
- 1Epigenetics and Progenitor Cells Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA;
- 2Colorado State University, Fort Collins, Colorado 80523, USA
Abstract
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.
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Footnotes
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↵3 Corresponding author.
↵E-MAIL zaret{at}fccc.edu; FAX (215) 379-4305.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1775509.
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Supplemental material is available at http://www.genesdev.org.
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- Received December 23, 2008.
- Accepted February 18, 2009.
- Copyright © 2009 by Cold Spring Harbor Laboratory Press
