Department of Biochemistry and Molecular Biology, Paul D. Coverdell Center for Biomedical and Health Sciences, The University of Georgia, Athens, Georgia 30602.
Cold Spring Harb Perspect Med. 2013 Dec 1;3(12):a014381. doi: 10.1101/cshperspect.a014381.
MYC and MYCN have been directly implicated in the transcriptional regulation of several thousand genes in pluripotent stem cells and possibly contribute to the activity of all transcribed genes. Control of transcription by a pause-release mechanism, recruitment of positive and negative epigenetic regulators, and a general role in transcriptional amplification have all been implicated as part of the broad, overarching mechanism by which MYC controls stem cell biology. As would be anticipated from the regulation of so many genes, MYC is involved in a wide range of cellular processes including cell-cycle control, metabolism, signal transduction, self-renewal, maintenance of pluripotency, and control of cell fate decisions. MYC transcription factors also have clear roles in cell reprogramming and establishment of the pluripotent state. The mechanism by which MYC accomplishes this is now being explored and promises to uncover unexpected facets of general MYC regulation that are likely to be applicable to cancer biology. In this work we review our current understanding of how MYC contributes to the maintenance and establishment of pluripotent cells and how it contributes to early embryonic development.
MYC 和 MYCN 直接参与了多能干细胞中数千个基因的转录调控,并可能有助于所有转录基因的活性。暂停释放机制的转录控制、募集正和负的表观遗传调节剂,以及在转录放大中的一般作用,都被认为是 MYC 控制干细胞生物学的广泛的、总体的机制的一部分。从对如此多的基因的调控中可以预期,MYC 参与了广泛的细胞过程,包括细胞周期控制、代谢、信号转导、自我更新、多能性维持和细胞命运决定的控制。MYC 转录因子在细胞重编程和多能状态的建立中也有明确的作用。MYC 实现这一目标的机制正在被探索,并有望揭示一般 MYC 调控的意想不到的方面,这些方面可能适用于癌症生物学。在这项工作中,我们回顾了我们目前对 MYC 如何有助于维持和建立多能细胞以及它如何有助于早期胚胎发育的理解。