Proudhon Charlotte, Hao Bingtao, Raviram Ramya, Chaumeil Julie, Skok Jane A
Department of Pathology, New York University School of Medicine, New York, USA.
Institut Curie, CNRS UMR3215, INSERM U934, Paris, France.
Adv Immunol. 2015;128:123-82. doi: 10.1016/bs.ai.2015.07.003. Epub 2015 Aug 20.
Given their essential role in adaptive immunity, antigen receptor loci have been the focus of analysis for many years and are among a handful of the most well-studied genes in the genome. Their investigation led initially to a detailed knowledge of linear structure and characterization of regulatory elements that confer control of their rearrangement and expression. However, advances in DNA FISH and imaging combined with new molecular approaches that interrogate chromosome conformation have led to a growing appreciation that linear structure is only one aspect of gene regulation and in more recent years, the focus has switched to analyzing the impact of locus conformation and nuclear organization on control of recombination. Despite decades of work and intense effort from numerous labs, we are still left with an incomplete picture of how the assembly of antigen receptor loci is regulated. This chapter summarizes our advances to date and points to areas that need further investigation.
鉴于其在适应性免疫中的关键作用,抗原受体基因座多年来一直是分析的焦点,并且是基因组中少数几个研究最为深入的基因之一。对它们的研究最初带来了对线性结构以及赋予其重排和表达控制的调控元件特征的详细了解。然而,DNA荧光原位杂交(FISH)和成像技术的进步,再加上探究染色体构象的新分子方法,使得人们越来越认识到线性结构只是基因调控的一个方面,近年来,重点已转向分析基因座构象和核组织对重组控制的影响。尽管经过了数十年的努力以及众多实验室的高强度工作,但我们对于抗原受体基因座的组装是如何受到调控的仍只有不完整的认识。本章总结了我们迄今取得的进展,并指出了需要进一步研究的领域。