Fig. 9. A simplified model of MSH1-associated phenotypic plasticity.

Stress-associated suppression of MSH1 expression alters conditions within the sensory plastid of epidermal and vascular parenchyma cells^20,58. These changes involve at least two retrograde signaling pathways to the nucleus, one including redox and calcium signaling²⁰ and the other tocopherol-mediated modulation of the PAP phosphonucleotide as a mediator of miRNA regulation^58,77. Nuclear response to sensory plastid perturbation is dependent on HDA6 and MET1 and includes genome-wide cytosine methylation repatterning and altered expression of integrated stress response networks. Specificity factors (gray oval) have been identified that associate with, and recruit, HDA6 to target loci that participate in the MSH1 effect⁴⁵. The heritability of this repatterning may be influenced by proximity of TEs to the target loci and the nature of HDA6 activity. Transgenerational memory induced by MSH1 suppression gives rise, through crossing or grafting, to progeny with markedly enhanced growth vigor and resilience phenotypes^15,17,59,60. Gene promoters are shown as blue bars; target genes are shown by generic gray bar. Solid lines reflect data shown by our group; dashed lines reflect data published by other groups that are consistent with MSH1 data (past and present). This figure was created by the authors.