Plants, compared to animals, have an extra energy-producing organelle besides the mitochondria: the plastid. They both contain a small number of genes in their genomes: 120 in the plastid and 37 in the mitochondria, respectively. But the nuclear genome is outnumbered by organellar genomes by as much as 1 to 5,000. Retrograde pathways have been defined in order to describe the existing cross-talk between the organelles and the nucleus, and to understand how nuclear gene expression (NGE) is modeled according to signals received from both organelles. Mutants have been widely used to explain this phenomenon. But their potential is limmited because the genes identified to respond to retrograde signaling are linked to a single original stimulus, which is a mutation. However, cytolines represent a better model to study the effect of cytoplasm (including it’s organellar genomes). By repeated backcrosses one can transfer the nucleus from a donor line (used as male/pollen donor) to several other cytoplasms, thus creating isonuclear lines (or cytolines). Maize is a model plant that is best suited for studies on NGE, circumventing the shortcomings of mutants, by means of its cytolines. No study so far has used NGS technology to sequence the whole transcriptome in such lines, but rather phenotypic observations, microarray, and metabolomics approaches have been applied. Here, we transferred the nucleus of a donor line into two other cytoplasmic environments of the same species (Zea mays ssp. mays), through at least 10 back-crosses, thus creating three cytolines. Their transcriptome was sequenced using an Illumina HiSeq2500 instrument. We identified 96 nuclear genes that could potentially function as master switches under the direct control of the retrograde signaling pathways. More importantly, these genes are not differentially regulated as a result of mutation, nor any kind of stress. They are rather key players of the cytoplasm-to-nucleus communication in a normal state of the cell. We also identified orthologous genes in four other grasses and Arabidopsis thaliana, hinting towards a general mechanism in plants, where the retrograde signaling pathways target these key nuclear genes.