Ewe Chee Kiang, Torres Cleuren Yamila N, Flowers Sagen E, Alok Geneva, Snell Russell G, Rothman Joel H
Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93117.
Neuroscience Research Institute, University of California, Santa Barbara, CA 93117.
Proc Natl Acad Sci U S A. 2020 Jun 16;117(24):13637-13646. doi: 10.1073/pnas.1920343117. Epub 2020 Jun 1.
Gene regulatory networks (GRNs) that direct animal embryogenesis must respond to varying environmental and physiological conditions to ensure robust construction of organ systems. While GRNs are evolutionarily modified by natural genomic variation, the roles of epigenetic processes in shaping plasticity of GRN architecture are not well understood. The endoderm GRN in is initiated by the maternally supplied SKN-1/Nrf2 bZIP transcription factor; however, the requirement for SKN-1 in endoderm specification varies widely among distinct wild isotypes, owing to rapid developmental system drift driven by accumulation of cryptic genetic variants. We report here that heritable epigenetic factors that are stimulated by transient developmental diapause also underlie cryptic variation in the requirement for SKN-1 in endoderm development. This epigenetic memory is inherited from the maternal germline, apparently through a nuclear, rather than cytoplasmic, signal, resulting in a parent-of-origin effect (POE), in which the phenotype of the progeny resembles that of the maternal founder. The occurrence and persistence of POE varies between different parental pairs, perduring for at least 10 generations in one pair. This long-perduring POE requires piwi-interacting RNA (piRNA) function and the germline nuclear RNA interference (RNAi) pathway, as well as MET-2 and SET-32, which direct histone H3K9 trimethylation and drive heritable epigenetic modification. Such nongenetic cryptic variation may provide a resource of additional phenotypic diversity through which adaptation may facilitate evolutionary changes and shape developmental regulatory systems.
指导动物胚胎发育的基因调控网络（GRNs）必须对不断变化的环境和生理条件做出反应，以确保器官系统的稳健构建。虽然GRNs通过自然基因组变异在进化上发生改变，但表观遗传过程在塑造GRN结构可塑性方面的作用尚未得到充分理解。秀丽隐杆线虫中的内胚层GRN由母体提供的SKN-1/Nrf2 bZIP转录因子启动；然而，由于隐性遗传变异的积累导致快速的发育系统漂移，不同的秀丽隐杆线虫野生型在内胚层特化中对SKN-1的需求差异很大。我们在此报告，由短暂发育滞育刺激的可遗传表观遗传因素也是内胚层发育中对SKN-1需求的隐性变异的基础。这种表观遗传记忆从母系生殖系遗传而来，显然是通过核信号而非细胞质信号，从而产生亲本来源效应（POE），其中后代的表型类似于母本创始者的表型。POE的出现和持续时间在不同的亲本对之间有所不同，在一对亲本中持续至少10代。这种长期持续的POE需要与piwi相互作用的RNA（piRNA）功能和生殖系核RNA干扰（RNAi）途径，以及指导组蛋白H3K9三甲基化并驱动可遗传表观遗传修饰的MET-2和SET-32。这种非遗传的隐性变异可能提供额外的表型多样性资源，通过这种资源，适应性可能促进进化变化并塑造发育调控系统。
