CFDP1 是人源 SRCAP 染色质重塑复合物沉积组蛋白变体 H2A.Z 所必需
CFDP1 is required for histone variant H2A.Z deposition by the human SRCAP chromatin remodeling complex
人源 SRCAP 复合物（SRCAP-C）的 H2A.Z 二聚体交换依赖 CFDP1，CFDP1 缺失会使 hiPSCs 全基因组 H2A.Z、H3K27me3 与 H3K4me3 沉积下降。研究者通过生化重构与表征发现，CFDP1 以盐浓度依赖的方式与 SRCAP-C 弱相互作用，并刺激重构复合物的基础 ATPase 活性，提示其调控内在催化活性。在人诱导多能干细胞中敲缺 CFDP1 后，上述修饰整体减少，同时原本带有这些修饰的发育基因上调。
来源：Nucleic Acids Research · doi.org
Craniofacial Developmental Protein 1 (CFDP1) is a member of the evolutionarily conserved family of Bucentaur (BCNT) proteins and is required for cell survival and differentiation during tooth development. Its yeast homolog is involved in histone variant H2A.Z deposition by the yeast SWR1C remodeler. Direct connections between CFDP1, H2A.Z deposition, and the mammalian SWR1 homolog, Snf2-Related CREBBP Activator Protein (SRCAP), are poorly understood. Here, we perform detailed biochemical reconstitution and characterization of the human SRCAP complex (SRCAP-C). We find that CFDP1 weakly interacts with SRCAP-C in a salt concentration-dependent manner and is essential for H2A.Z dimer exchange by SRCAP-C. We show that CFDP1 stimulates the basal ATPase activity of reconstituted SRCAP-C, suggesting a requirement for CFDP1 in regulating intrinsic catalytic ATPase activity. Additionally, CFDP1 deficiency in human induced pluripotent stem cells (hiPSCs) leads to a genome-wide reduction of H2A.Z, H3K27me3, and H3K4me3 deposition, accompanied by the upregulation of developmental genes normally marked by these modifications. Taken together, our results provide mechanistic insights into how CFDP1 regulates histone variant H2A.Z deposition by SRCAP-C. Given mutations in the SRCAP gene cause Floating-Harbor syndrome, a rare, dominant developmental disorder, our study provides an additional link between craniofacial development and SRCAP-mediated H2A.Z deposition.