增强子是一类广受关注的调控元件，对于组织特异性基因表达谱的建立至关重要。一般认为活性增强子携带H3K4me1等组蛋白修饰，而H3K4me3修饰主要出现在基因启动子。近年一些研究报道了特殊情况下H3K4me3修饰在增强子上的出现，说明对该修饰与增强子之间的联系仍急需进一步全面系统的研究。申请人基于海量组学数据的整合分析和计算建模，发现许多血液和淋巴细胞中大量增强子被H3K4me3标记，并且它们相对其它增强子具有不同的转录因子组合和增强子RNA转录水平等特征。在此基础上，本项目拟系统比较H3K4me3标记的活性增强子与其它增强子之间的差异，定量刻画该修饰与增强子上其它表观修饰以及增强子活性之间的关联，发掘在血液和淋巴细胞中调控增强子上H3K4me3修饰水平的表观因子，深入解析该修饰在血液和淋巴细胞中选择性大范围标记活性增强子的功能影响和分子机制，进一步完善对于增强子表观图象的认识。

Enhancers are an important class of regulatory elements and are widely studied in recent years. They can positively regulate the transcription of downstream genes, and play a vital role in the establishment of tissue-specific transcriptional programs in higher organisms. In general, active enhancers are marked by several related histone modifications including H3K4me1 and H3K27ac, while H3K4me3 modification typically appears at gene promoters. Several recent studies reported that in some special conditions H3K4me3 can also appears on enhancers, but it’s still unclear whether H3K4me3 is naturally linked with the functional activity of enhancers. Based on integrative analysis of a large set of omics data and computational modeling, we found in many blood cell lineages a large fraction of active enhancers carry considerable H3K4me3 mark, and these enhancers generally have different transcription factor binding pattern and enhancer RNA transcription level compared to the other active enhancers. Based on these findings, we plan to systematically study the functional difference between the enhancers marked and not marked by H3K4me3, and quantitatively model the correlation between the level of H3K4me3 mark and that of other related epigenetic marks at enhancers as well as the functional activity of enhancers, detect the epigenetic factors regulating enhancer H3K4me3 levels in blood cell lineages, and dissect the functional impact of the selective appearance of H3K4me3 mark on many enhancers in these cells as well as the underlying molecular mechanism, which can greatly help to improve our knowledge of the epigenetic landscape of enhancer elements as well as how they carry out their functions.