Feng Yingying, Chen Sizhuo, Zhou Mengqi, Zhang Jin, Min Jinrong, Liu Ke
Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, PR China.
Heliyon. 2022 Jul 6;8(7):e09873. doi: 10.1016/j.heliyon.2022.e09873. eCollection 2022 Jul.
BAZ2B is a regulatory subunit of the ISWI (Imitation Switch) remodeling complex and engages in nucleosome remodeling. Loss-of-function and haploinsufficiency of BAZ2B are associated with different diseases. BAZ2B is a large multidomain protein. In addition to the epigenetic reader domains plant homeodomain (PHD) and bromodomain (BRD), BAZ2B also has a Tip5/ARBP/MBD (TAM) domain. Sequence alignment revealed that the TAM domains of BAZ2A and BAZ2B share 53% sequence identity. How the BAZ2A TAM domain bound with DNA has been characterized recently, however, the DNA binding ability and methylation preference, as well as the structural basis of the BAZ2B TAM domain are not studied yet. In this study, we measured the DNA binding affinity of the TAM domain of BAZ2B, and also determined its apo crystal structure. We found that the TAM domains of BAZ2A and BAZ2B adopt almost the same fold, and like BAZ2A, the BAZ2B TAM domain also binds to dsDNA without methyl-cytosine preference, implying that the BAZ2B TAM domain might recognize DNA in a similar binding mode to that of the BAZ2A TAM domain. These results provide clues for the biological function study of BAZ2B in the future.
BAZ2B是ISWI（模仿开关）重塑复合体的一个调节亚基，参与核小体重塑。BAZ2B的功能丧失和单倍剂量不足与不同疾病相关。BAZ2B是一种大型多结构域蛋白。除了表观遗传读取结构域植物同源结构域（PHD）和溴结构域（BRD）外，BAZ2B还具有Tip5/ARBP/MBD（TAM）结构域。序列比对显示，BAZ2A和BAZ2B的TAM结构域具有53%的序列同一性。最近已经对BAZ2A TAM结构域与DNA的结合方式进行了表征，然而，BAZ2B TAM结构域的DNA结合能力、甲基化偏好以及结构基础尚未得到研究。在本研究中，我们测量了BAZ2B TAM结构域的DNA结合亲和力，并确定了其无配体晶体结构。我们发现，BAZ2A和BAZ2B的TAM结构域具有几乎相同的折叠方式，并且与BAZ2A一样，BAZ2B TAM结构域也结合双链DNA，且对甲基化胞嘧啶没有偏好，这意味着BAZ2B TAM结构域可能以与BAZ2A TAM结构域相似的结合模式识别DNA。这些结果为未来BAZ2B的生物学功能研究提供了线索。
