Overview of the various epigenomic features involved in the regulation of gene expression. At the largest genomic scales, chromosomes segregate within 3D nuclear space into a nuclear lamina-associated, transcriptionally repressed B compartment and a transcriptionally active A compartment that occupies the nuclear interior. Within these compartments, cohesin and CTCF together form TADs through a process called loop extrusion. TADs are spatially insulated genomic regions that facilitate interactions between genes and their regulatory elements (e.g., promoters, enhancers). At the level of the chromatin fiber, DNA is wrapped around nucleosomes consisting of histone octamers that can be posttranslationally modified (e.g., acetylation, methylation). DNA itself can also carry methylation modifications. Nucleosome positioning and histone/DNA modifications, together with 3D chromatin architecture, shape a local chromatin environment that either supports or inhibits the recruitment of TFs and RNA polymerases to control gene transcription.