跳轉至內容
Merck
  • FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription.

FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription.

Cell (2008-03-25)
Mathieu Lupien, Jérôme Eeckhoute, Clifford A Meyer, Qianben Wang, Yong Zhang, Wei Li, Jason S Carroll, X Shirley Liu, Myles Brown
摘要

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.