Department of Genetics and Development, Columbia University Medical Center, New York, NY, USA.
Wiley Interdiscip Rev Syst Biol Med. 2012 May-Jun;4(3):273-83. doi: 10.1002/wsbm.1162. Epub 2012 Feb 14.
The T-box transcription factor Tbx3 plays multiple roles in normal development and disease. In order to function in different tissues and on different target genes, Tbx3 binds transcription factors or other cofactors specific to temporal or spatial locations. Examining the development of the mammary gland, limbs, and heart as well as the biology of stem cells and cancer provides insights into the diverse and common functions that Tbx3 can perform. By either repressing or activating transcription of target genes in a context-dependent manner, Tbx3 is able to modulate differentiation of immature progenitor cells, control the rate of cell proliferation, and mediate cellular signaling pathways. Because the direct regulators of these cellular processes are highly context-dependent, it is essential that Tbx3 has the flexibility to regulate transcription of a large group of targets, but only become a active on a small cohort of them at any given time or place. Moreover, Tbx3 must be responsive to the variety of different upstream factors that are present in different tissues. Only by understanding the network of genes, proteins, and molecules with which Tbx3 interacts can we hope to understand the role that Tbx3 plays in normal development and how its aberrant expression can lead to disease. Because of its myriad functions in disparate developmental and disease contexts, Tbx3 is an ideal candidate for a systems-based approach to genetic function and interaction.
T 盒转录因子 Tbx3 在正常发育和疾病中发挥多种作用。为了在不同组织和不同靶基因上发挥功能，Tbx3 结合特定于时间或空间位置的转录因子或其他共因子。研究乳腺、肢体和心脏的发育以及干细胞和癌症的生物学为 Tbx3 可以执行的多样化和共同功能提供了深入了解。Tbx3 通过在上下文相关的方式中抑制或激活靶基因的转录，能够调节未成熟祖细胞的分化、控制细胞增殖的速度，并介导细胞信号通路。由于这些细胞过程的直接调节剂高度依赖于上下文，因此 Tbx3 必须具有灵活性来调节一大组靶基因的转录，但只能在任何特定时间或地点在一小部分靶基因上变得活跃。此外，Tbx3 必须对不同组织中存在的各种不同的上游因子做出响应。只有了解与 Tbx3 相互作用的基因、蛋白质和分子网络，我们才能希望了解 Tbx3 在正常发育中的作用以及其异常表达如何导致疾病。由于 Tbx3 在不同的发育和疾病背景下具有众多功能，因此它是一种用于基于系统的遗传功能和相互作用的理想候选者。
