转移相关蛋白MTA1是转录抑制复合体NuRD的特征组分，据报道，MTA1赖氨酸位点的甲基化使其维持与NuRD的相互作用，而MTA1的精氨酸位点能否被甲基化酶修饰，以及这种修饰对其生物学功能有何影响，目前尚未知晓。申请者前期研究证实，转录因子ZEB2能招募MTA1/NuRD，促发乳腺癌的转移。而在胰腺癌中，MTA1通过与SET8相互作用，促进胰腺癌细胞血管新生。申请者在预实验中通过亲和纯化-质谱、快速蛋白液相色谱等蛋白质组学的方法筛选出MTA1与精氨酸甲基化酶CARM1存在相互作用，且能被其甲基化修饰。本项目将进一步研究甲基化修饰后的MTA1能招募新的染色质重塑复合体NuRF，两者共同调控新的下游靶基因，揭示MTA1/NuRD抑制复合体向MTA1/NuRF激活复合体的动态转换，并在细胞、动物及乳腺癌患者组织中，研究MTA1/NuRF复合体的生物学意义，为寻找新的乳腺癌药物靶点提供线索。

Metastasis-Associated Protein MTA1 is a characteristic subunit of the transcription repression complex NuRD. As reported, methylation at the lysine site of MTA1 is required for its interaction with the NuRD repressor complex. However, whether the arginine site of MTA1 could be modified by methyltransferase and how this modification could affect its biological function is unknown. Our previous studies confirmed that ZEB2 could recruit MTA1/NuRD and promote the breast cancer metastasis. Furthermore, in pancreatic cancer, by interacting with SET8, MTA1 promotes angiogenesis. In the preliminary experiment, using affinity purification and mass spectrometry combined with fast protein liquid chromatography system, we revealed the interaction between CARM1 and MTA1. Interestingly, we found MTA1 could be methylated by CARM1. In this study, we will further investigate that the methylated MTA1 could recruit new chromatin remodeling complex NuRF to regulate new downstream target genes, elucidating a new perspective to the molecular governance of the dynamic transformation from MTA1/NuRD repression complex to MTA1/NuRF activation complex. We will study the biological significance of MTA1/NuRF complex from cell, animal level and breast cancer tissues samples in order to provide potential novel therapeutic targets for breast cancer.