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转录因子旁系同源物选择性调控免疫发育
作者:小柯机器人 发布时间:2019/8/27 13:23:02

英国MRC伦敦医学科学研究所Matthias Merkenschlager研究组的一项最新研究揭示,转录因子旁系同源物在免疫系统发育中选择性调控基因表达。相关论文2019年8月25日在线发表于国际学术期刊《自然—免疫学》。

研究人员在希望了解朗格汉斯细胞和诱导型调节性T细胞分化过程中RUNX旁系同源物的选择性表达可能支持哪些细胞类型特异性生物事件。研究人员揭示了RUNX旁系同源物之间的功能不对等。天然旁系同源物的选择性表达允许转录因子活性与外在信号的整合,而非天然旁系同源物即使在不存在外源诱导物的情况下也强制进行分化。DNA结合亲和力由另外高度保守的RUNT结构域内的不同氨基酸控制,并且进化重构表明RUNT结构域残基倾向于次最大强度的收敛。因此,在特化细胞类型中重复基因的选择性表达可以与获得的功能差异协同作用,从而在哺乳动物免疫系统中实现适当的基因表达、谱系选择和分化。

据悉,在多细胞生物中,重复的基因可以通过组织特异性基因表达模式变得不同,例如具有明显功能冗余的RUNX转录因子旁系同源物的高度调节性表达。

附:英文原文

Title: Selective deployment of transcription factor paralogs with submaximal strength facilitates gene regulation in the immune system

Author: Ludovica Bruno, Vijendra Ramlall, Romain A. Studer, Stephan Sauer, David Bradley, Gopuraja Dharmalingam, Thomas Carroll, Mohamed Ghoneim, Michal Chopin, Stephen L. Nutt, Sarah Elderkin, David S. Rueda, Amanda G. Fisher, Trevor Siggers, Pedro Beltrao, Matthias Merkenschlager

Issue&Volume: 2019-08-26

Abstract: In multicellular organisms, duplicated genes can diverge through tissue-specific gene expression patterns, as exemplified by highly regulated expression of RUNX transcription factor paralogs with apparent functional redundancy. Here we asked what cell-type-specific biologies might be supported by the selective expression of RUNX paralogs during Langerhans cell and inducible regulatory T cell differentiation. We uncovered functional nonequivalence between RUNX paralogs. Selective expression of native paralogs allowed integration of transcription factor activity with extrinsic signals, while non-native paralogs enforced differentiation even in the absence of exogenous inducers. DNA binding affinity was controlled by divergent amino acids within the otherwise highly conserved RUNT domain and evolutionary reconstruction suggested convergence of RUNT domain residues toward submaximal strength. Hence, the selective expression of gene duplicates in specialized cell types can synergize with the acquisition of functional differences to enable appropriate gene expression, lineage choice and differentiation in the mammalian immune system.

DOI: 10.1038/s41590-019-0471-5

Source:https://www.nature.com/articles/s41590-019-0471-5

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex