Gene expression regulatory mechanisms. Gene regulation in the eukaryotic cell nucleus involves different mechanisms that occur simultaneously at different spatial scales and biological contexts. These mechanisms include chromatin looping to allow contact between cis regulatory elements like enhancers and promoters, so recruitment of the transcriptional machinery can be facilitated; non coding RNA modulation of gene expression and silencing; methylation of DNA as an steric impediment to TFs binding, thus silencing transcription; and histone post transcriptional modifications that contribute to the electrostatic landscape of chromatin and encourage (e.g., H3K4me1 and H3K27ac that mark enhancer sequences or H3K4me3 that protects promoters from DNA methylation) or deter (e.g., H3K27me3 and H3K9me3 that mark heterochromatin) transcriptional processes. To date, the cooperativity and feedback between them remains to be fully characterized. (Image created with BioRender, https://biorender.com/).