The nuclear genome is outnumbered by the genomes of cellular organelles at a ratio of 1 in 5,000. Nuclear gene expression (NGE) is regulated by retrograde signalling (CRS) pathways from organelles to the nucleus. To decipher this mode of EGN control, plants mutant for one of the CRS components have been used predominantly so that it remains unclear what mechanisms are at work in a non-mutant cell. These mechanisms may change the paradigm with which we currently operate to explain organelle-nucleus communication. To circumvent the problem of using these less informative mutants we propose the use of maize isonuclear lines, whose agronomic/morphological traits are directly related to CRS. So far, however, no study has used NGS technology to sequence the entire transcriptome of an isonuclear line and thus gain insight into the EGN. In this context, we wish to embark on an in-depth analysis of CRS and use the acquired knowledge to explain important agronomic traits of maize at the molecular level. We will also attempt to answer the question whether methylation plays any role in the regulation of EGN depending on the surrounding cytoplasmic environment. In addition, we will investigate whether extant polymorphism at the level of cellular organelle genomes intervenes in this process, by sequencing them in isonuclear lines included in the NGS transcriptomic analysis.