The Nucleosome Map of the Mammalian Liver

Mammalian genomes contain billions of basepairs of DNA that must be highly compacted as chromatin to fit into the nano-scale of the nucleus, but yet be accessible to allow for transcription to occur. Binding to nucleosomal DNA is critical for ÔpioneerÕ transcription factors such as Foxa1 and Foxa2 to regulate chromatin structure and gene activation. Here we report the genome-wide map of nucleosome positions in the mouse liver, with emphasis on transcriptional start sites, CpG islands, Foxa2 binding sites, and their correlation with gene expression. Despite the heterogeneity of liver tissue, we could clearly discern the nucleosome pattern of the predominant liver cell, the hepatocyte. By analyzing nucleosome occupancy and the distributions of heterochromatin protein 1 (Hp1), CBP, and p300 in Foxa1/2-deficient livers we find, surprisingly, that the maintenance of nucleosome position and chromatin structure surrounding Foxa2 binding sites is independent of Foxa1/2. Original data matrix is in the archive: E-MTAB-514.additional.zip哺乳动物基因组包含数十亿碱基对的DNA，这些DNA必须以染色质形式高度压缩，以适配细胞核的纳米级尺度，但同时又需保持可及性以保障转录过程顺利进行。结合核小体DNA对于诸如Foxa1与Foxa2这类先锋（pioneer）转录因子调控染色质结构与基因激活至关重要。本研究报道了小鼠肝脏全基因组范围内的核小体定位图谱，重点关注转录起始位点、CpG岛、Foxa2结合位点，及其与基因表达的相关性。尽管肝脏组织存在异质性，我们仍可清晰辨别占主导的肝脏细胞——肝细胞的核小体模式。通过分析Foxa1/2缺陷型肝脏中核小体占据情况，以及异染色质蛋白1（Hp1）、CBP与p300的分布特征，我们意外发现，Foxa2结合位点周围的核小体定位与染色质结构的维持，并不依赖于Foxa1/2。原始数据矩阵存档于E-MTAB-514.additional.zip。