FoxA1 Translates Epigenetic Signatures into Enhancer-Driven Lineage-Specific Transcription
- 作者：Mathieu Lupien ; Jé ; rô ; me Eeckhoute ; Clifford A. Meyer ; Qianben Wang ; Yong Zhang ; Wei Li ; Jason S. Carroll ; X. Shirley Liu ; Myles Brown
- 关键词：DEVBIO ; DNA
- 刊名：Cell
- 出版年：2008
- 期刊代码：50_00928674
- 类别：med
- 出版时间：21 March 2008
- 卷：132
- 期：6
- 页码：958-970
- 文件大小：1673 K
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.