[HTML][HTML] FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription

M Lupien, J Eeckhoute, CA Meyer, Q Wang, Y Zhang… - Cell, 2008 - cell.com
Cell, 2008cell.com
Complex organisms require tissue-specific transcriptional programs, yet little is known about
how these are established. The transcription factor FoxA1 is thought to contribute to gene
regulation through its ability to act as a pioneer factor binding to nucleosomal DNA. Through
genome-wide positional analyses, we demonstrate that FoxA1 cell type-specific functions
rely primarily on differential recruitment to chromatin predominantly at distant enhancers
rather than proximal promoters. This differential recruitment leads to cell type-specific …
Summary
Complex organisms require tissue-specific transcriptional programs, yet little is known about how these are established. The transcription factor FoxA1 is thought to contribute to gene regulation through its ability to act as a pioneer factor binding to nucleosomal DNA. Through genome-wide positional analyses, we demonstrate that FoxA1 cell type-specific functions rely primarily on differential recruitment to chromatin predominantly at distant enhancers rather than proximal promoters. This differential recruitment leads to cell type-specific changes in chromatin structure and functional collaboration with lineage-specific transcription factors. Despite the ability of FoxA1 to bind nucleosomes, its differential binding to chromatin sites is dependent on the distribution of histone H3 lysine 4 dimethylation. Together, our results suggest that methylation of histone H3 lysine 4 is part of the epigenetic signature that defines lineage-specific FoxA1 recruitment sites in chromatin. FoxA1 translates this epigenetic signature into changes in chromatin structure thereby establishing lineage-specific transcriptional enhancers and programs.
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