Kazantseva Jekaterina, Palm Kaia
Protobios LLC, Mäealuse 4, Tallinn 12618, Estonia.
Int J Mol Sci. 2014 Sep 19;15(9):16680-97. doi: 10.3390/ijms150916680.
Development is a highly controlled process of cell proliferation and differentiation driven by mechanisms of dynamic gene regulation. Specific DNA binding factors for establishing cell- and tissue-specific transcriptional programs have been characterised in different cell and animal models. However, much less is known about the role of "core transcription machinery" during cell differentiation, given that general transcription factors and their spatiotemporally patterned activity govern different aspects of cell function. In this review, we focus on the role of TATA-box associated factor 4 (TAF4) and its functional isoforms generated by alternative splicing in controlling lineage-specific differentiation of normal mesenchymal stem cells and cancer stem cells. In the light of our recent findings, induction, control and maintenance of cell differentiation status implies diversification of the transcription initiation apparatus orchestrated by alternative splicing.
发育是一个由动态基因调控机制驱动的、高度受控的细胞增殖和分化过程。在不同的细胞和动物模型中,已经鉴定出用于建立细胞和组织特异性转录程序的特定DNA结合因子。然而,鉴于一般转录因子及其时空模式化的活性控制着细胞功能的不同方面,关于“核心转录机制”在细胞分化过程中的作用,我们所知甚少。在这篇综述中,我们聚焦于TATA盒相关因子4(TAF4)及其通过可变剪接产生的功能异构体在控制正常间充质干细胞和癌症干细胞的谱系特异性分化中的作用。根据我们最近的研究结果,细胞分化状态的诱导、控制和维持意味着由可变剪接精心编排的转录起始装置的多样化。