目前已被证实的组蛋白修饰位点和修饰类型有很多，尽管其确切的生物学意义尚不清楚，但是不同组蛋白修饰在基因转录调控中的相互协调作用越来越受关注。我们在之前研究中分离纯化了含9个亚基的人MOF-NSL组蛋白乙酰基转移酶，并鉴定其能够乙酰基化组蛋白H4上第5、8和16赖氨酸位点的底物特异性。在体外实验我们还证实NSL复合物可以通过乙酰基化H4来促进MLL/SET催化H3K4me2活性，而且这两种复合物在细胞中协同调控MOF的靶基因ANKRD2。本项目将延续前期研究内容，拟通过RNA-Seq和ChIP-Seq检测及分析，明确NSL和MLL/SET两种复合物及其相应组蛋白修饰在基因组上的分布情况，弄清MLL-SET复合物与不同H4乙酰基化修饰状态染色质的结合模式，筛选能被两种复合物共同调控、并与肿瘤发生密切相关的基因，阐明两种复合物对其转录调控的协同机制，为后续相关靶向治疗药物的研发提供实验基础。

Currently, many types of histone modification and modified sites have been proven. Although the specific biological functions still need to be studied, research evidence about the crosstalk between different chromatin modifying enzymes has been increased, suggesting the importance of co-ordination between histone modifications in gene transcriptional regulation. In previous study, we purified and characterized the MOF-NSL histone acetyltransferase complex which included nine protein subunits in human cells. We also clarified that the MOF-NSL complex can acetylate histone H4K5/K8/K16. Furthermore, we verified that MOF-NSL complex could facilitate H3K4me2 by MLL/SET methyltransferase through acetylating histone H4 in vitro. In addtion, the MOF target gene ANKRD2 was co-regulated by MOF-NSL and MLL/SET complexes. In this study, based on RNA-Seq and ChIP-Seq data analysis, we will: 1) confirm the genome-wide distribution of the MOF-NSL and MLL/SET complexes and their corresponding histone modifications; 2) verify the binding mode between the complexes and the nucleosomal chromatin under different histone H4 modification conditions; 3) acquire genes that are regulated by both complexes and closely related to tumorigenesis. 4) further demonstrate the crosstalk between two complexes in gene transcriptional regulation and their mechanism. Our study will provide experimental evidence and theoretical basis for developing the gene-targeted medicine in future studies.