PHF6的突变是引起Borjeson-Forssman-Lehmann 综合症（BFLS）和急性T淋巴细胞白血病（T-ALL）的重要原因之一。近来，研究报道PHF6可以直接结合核仁蛋白UBF调控核糖体DNA（rDNA）的转录，这为理解PHF6的功能提供了重要线索。但我们前期研究表明PHF6是一个潜在的组蛋白表观遗传调节蛋白。本课题拟通过鉴定和深入研究PHF6的组蛋白甲基化结合位点、相互作用的组蛋白修饰酶以及两者互作对核仁组蛋白的调控作用，系统阐明PHF6调控组蛋白表观遗传状态的分子机制。同时，研究PHF6突变引起核仁组蛋白修饰异常的分子机制，探索其基因突变与T-ALL发生的关系。此外，还将应用全基因组shRNA 文库技术鉴定PHF6或rDNA转录抑制剂联合致死靶点，为PHF6相关T-ALL的治疗提供新靶点和新途径。

The PHF6 mutations are closely related to the genesis of BLFS (Borjeson-Forssman-Lehmann syndrome) and T-ALL (T-lineage acute lymphoblastic leukemia). A previous study report that PHF6 can regulate the transcription of ribosomal DNA (rDNA) through directly interacting with UBF (Upstream binding factor), which provides an important clue for understanding the cellular function of PHF6. Here,we presume that PHF6 may play an important role in epigenetic regulation of nucleolar histone. In this study, we will identify the histone methylation sites specifcally recognized by PHF6, find the histone modification complexes which interact with PHF6 in nucleolus, and investigate the regulation role of PHF6-associated complexes on histone epigenetic states. Furthermore, we will also investigate whether PHF6 mutations can induce aberrant histone modification at the rDNA gene locus in leukemia cells, and anylaze the reason of abbrrant modifications. In additon, we expect to identify the synthetic lethal targtets with PHF6 or rDNA inhibitor for the treatment of PHF6-mutated T-ALL leukemia.