Pagliaroli Luca, Trizzino Marco
Department of Biochemistry and Molecular Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States.
Front Cell Dev Biol. 2021 Mar 4;9:643361. doi: 10.3389/fcell.2021.643361. eCollection 2021.
Organismal development is a process that requires a fine-tuned control of cell fate and identity, through timely regulation of lineage-specific genes. These processes are mediated by the concerted action of transcription factors and protein complexes that orchestrate the interaction between -regulatory elements (enhancers, promoters) and RNA Polymerase II to elicit transcription. A proper understanding of these dynamics is essential to elucidate the mechanisms underlying developmental diseases. Many developmental disorders, such as Coffin-Siris Syndrome, characterized by growth impairment and intellectual disability are associated with mutations in subunits of the SWI/SNF chromatin remodeler complex, which is an essential regulator of transcription. and its paralog encode for the two largest, mutually exclusive, subunits of the complex. Mutations in and, especially, are recurrently associated with a very wide array of developmental disorders, suggesting that these two SWI/SNF subunits play an important role in cell fate decision. In this mini-review we therefore discuss the available scientific literature linking and to cell fate determination, pluripotency maintenance, and organismal development.
生物体发育是一个需要通过对谱系特异性基因进行适时调控来精确控制细胞命运和特性的过程。这些过程由转录因子和蛋白质复合物的协同作用介导,它们协调调控元件(增强子、启动子)与RNA聚合酶II之间的相互作用以引发转录。正确理解这些动态对于阐明发育性疾病的潜在机制至关重要。许多发育障碍,如以生长发育迟缓及智力残疾为特征的科芬-西里斯综合征,都与SWI/SNF染色质重塑复合物亚基的突变有关,该复合物是转录的重要调节因子。 及其旁系同源物编码该复合物的两个最大的、相互排斥的亚基。 和 中的突变,尤其是 中的突变,经常与各种各样的发育障碍相关,这表明这两个SWI/SNF亚基在细胞命运决定中起重要作用。因此,在本综述中,我们讨论了将 和 与细胞命运决定、多能性维持及生物体发育联系起来的现有科学文献。