Istituto Pasteur Italia-Fondazione Cenci Bolognetti and Dipartimento di Biologia e Biotecnologie "Charles Darwin", Sapienza Università di Roma, Italy.
Dipartimento di Biologia e Biotecnologie "Charles Darwin" Sapienza Università di Roma, Roma, Italy.
Sci Rep. 2017 Apr 3;7:45022. doi: 10.1038/srep45022.
The human Cranio Facial Development Protein 1 (Cfdp1) gene maps to chromosome 16q22.2-q22.3 and encodes the CFDP1 protein, which belongs to the evolutionarily conserved Bucentaur (BCNT) family. Craniofacial malformations are developmental disorders of particular biomedical and clinical interest, because they represent the main cause of infant mortality and disability in humans, thus it is important to understand the cellular functions and mechanism of action of the CFDP1 protein. We have carried out a multi-disciplinary study, combining cell biology, reverse genetics and biochemistry, to provide the first in vivo characterization of CFDP1 protein functions in human cells. We show that CFDP1 binds to chromatin and interacts with subunits of the SRCAP chromatin remodeling complex. An RNAi-mediated depletion of CFDP1 in HeLa cells affects chromosome organization, SMC2 condensin recruitment and cell cycle progression. Our findings provide new insight into the chromatin functions and mechanisms of the CFDP1 protein and contribute to our understanding of the link between epigenetic regulation and the onset of human complex developmental disorders.
人类颅面发育蛋白 1（Cfdp1）基因定位于 16q22.2-q22.3 染色体上，编码 CFDP1 蛋白，该蛋白属于进化上保守的 Bucentaur（BCNT）家族。颅面畸形是发育障碍的一种，具有特殊的生物医学和临床意义，因为它们是导致人类婴儿死亡和残疾的主要原因，因此了解 CFDP1 蛋白的细胞功能和作用机制非常重要。我们进行了一项多学科研究，结合细胞生物学、反向遗传学和生物化学，首次对 CFDP1 蛋白在人细胞中的功能进行了体内特征描述。我们发现 CFDP1 与染色质结合，并与 SRCAP 染色质重塑复合物的亚基相互作用。在 HeLa 细胞中用 RNAi 介导的 CFDP1 耗竭会影响染色体组织、SMC2 凝聚素募集和细胞周期进程。我们的发现为 CFDP1 蛋白的染色质功能和机制提供了新的见解，并有助于我们理解表观遗传调控与人类复杂发育障碍之间的联系。
