Department of Neuroscience, UT Southwestern Medical Center, Dallas, Texas, USA.
Curr Top Dev Biol. 2011;97:55-74. doi: 10.1016/B978-0-12-385975-4.00009-7.
Notch-dependent CSL transcription complexes control essential biological processes such as cell proliferation, differentiation, and cell-fate decisions in diverse developmental systems. The orthologous proteins CBF1/Rbpj (mammalian), Su(H) (Drosophila), and Lag-1 (Caenorhabditis elegans) compose the CSL family of sequence-specific DNA-binding transcription factors. The CSL proteins are best known for their role in canonical Notch signaling. However, CSL factors also form transcription complexes that can function independent of Notch signaling and include repression and activation of target gene transcription. Because the different complexes share CSL as a DNA-binding subunit, they can control overlapping sets of genes; but they can also control distinct sets when partnered with tissue-specific cofactors that restrict DNA-sequence recognition or stability of the DNA-bound complex. The Notch-independent functions of CSL and the processes they regulate will be reviewed here with a particular emphasis on the tissue-specific CSL-activator complex with the bHLH factor Ptf1a.
Notch 依赖性 CSL 转录复合物控制着各种发育系统中的基本生物学过程,如细胞增殖、分化和细胞命运决定。同源蛋白 CBF1/Rbpj(哺乳动物)、Su(H)(果蝇)和 Lag-1(秀丽隐杆线虫)组成了 CSL 家族的序列特异性 DNA 结合转录因子。CSL 蛋白以其在经典 Notch 信号中的作用而闻名。然而,CSL 因子也形成转录复合物,这些复合物可以独立于 Notch 信号发挥作用,包括靶基因转录的抑制和激活。由于不同的复合物共享 CSL 作为 DNA 结合亚基,它们可以控制重叠的基因集;但当与组织特异性共因子结合时,它们也可以控制不同的基因集,这些共因子限制 DNA 序列识别或 DNA 结合复合物的稳定性。本文将重点介绍与 bHLH 因子 Ptf1a 形成的组织特异性 CSL-激活复合物的 Notch 非依赖性 CSL 功能及其调控的过程。