An H3K27me3 demethylase-HSFA2 regulatory loop orchestrates transgenerational thermomemory in Arabidopsis

Abstract

Global warming has profound effects on plant growth and fitness. Plants have evolved sophisticated epigenetic machinery to respond quickly to heat, and exhibit transgenerational memory of the heat-induced release of post-transcriptional gene silencing (PTGS). However, how thermomemory is transmitted to progeny and the physiological relevance are elusive. Here we show that heat-induced HEAT SHOCK TRANSCRIPTION FACTOR A2 (HSFA2) directly activates the H3K27me3 demethylase RELATIVE OF EARLY FLOWERING 6 (REF6), which in turn derepresses HSFA2. REF6 and HSFA2 establish a heritable feedback loop, and activate an E3 ubiquitin ligase, SUPPRESSOR OF GENE SILENCING 3 (SGS3)-INTERACTING PROTEIN 1 (SGIP1). SGIP1-mediated SGS3 degradation leads to inhibited biosynthesis of trans-acting siRNA (tasiRNA). The REF6-HSFA2 loop and reduced tasiRNA converge to release HEAT-INDUCED TAS1 TARGET 5 (HTT5), which drives early flowering but attenuates immunity. Thus, heat induces transmitted phenotypes via a coordinated epigenetic network involving histone demethylases, transcription factors, and tasiRNAs, ensuring reproductive success and transgenerational stress adaptation.

Regulation of High-Temperature Stress Response by Small RNAs

“…miR319 is upregulated and TCP family genes are downregulated during HS (Hivrale et al 2016). ta-siRNAs also affect flowering time regulation (Liu et al 2019) (see later). In summary, the spectrum of sRNAome fine-tunes stress response both through positive and negative activities in order to mitigate the detrimental impact of heat and successfully accomplish reproduction.…”

“…Besides HSFA2, a growing number of stress memory factors have been discovered (Brzezinka et al 2018;Charng et al 2006;Lin et al 2014;Liu et al 2018;Meiri and Breiman 2009). Thermomemory was shown to be transmitted transgenerationally (Liu et al 2019). Micro RNAs (miRNA) and small interfering RNAs (siRNA) are intimately involved in high-temperature stress response and thermomemory.…”

“…Moderate heat stress (30°C) induces the epigenetic release of RNA silencing through inhibition of ta-siRNA biogenesis (Zhong et al 2013). It was shown recently that this pathway requires the activity of HSFA2, REF6, and SGIP1 (Liu et al 2019). HSFA2 transcriptionally activates RELATIVE OF EARLY FLOWERING 6 (REF6), an H3K27-demethylase gene (Lu et al 2011).…”

Mimulus sRNAs Are Wound Responsive and Associated with Transgenerationally Plastic Genes but Rarely Both

“…These lasting epigenetic modifications include DNA methylation, histone methylation and histone acetylation and can alter the RNA expression, chromatin accessibility and splicing that occurs proximal to these markings [ 1 , 2 , 3 ]. Additionally, these markings can be transmitted between mitotic and sometimes meiotic cell divisions [ 4 , 5 ] allowing developmental and environmental cues to leave a lasting impact on a cell lineage, altering the development of cells in later life history stages or even in the next generation.…”

“…Meiotic transmission of epigenetic markings resulting from environmental cues provides a mechanism through which plastic responses to the environment can be transmitted from one generation to the next (transgenerational plasticity [ 6 ]). While plant germline cells do undergo a number of rounds of epigenetic reprogramming prior to the formation of a new seed [ 7 ], it is clear that environmental conditions experienced by parents can alter phenotypes [ 8 , 9 , 10 , 11 ], epigenetic profiles [ 4 , 10 , 12 , 13 ] and gene expression [ 14 , 15 , 16 ] in the next generation. Importantly, autocorrelation between offspring and parent environment can favor mechanisms that establish such patterns of transgenerational plasticity [ 17 , 18 ], perhaps leading to natural selection that either favors or disfavors this transmission depending on local environmental patterns [ 11 ].…”