To differentiate between heterochromatin and euchromatin, light microscopy was traditionally used. This allowed the observation of lighter (euchromatic) and darker, more dense (heterochromatic) regions within the nucleus during interphase. As this method was not quantitative, and did not allow sequencing, developments have occurred.
Third generation sequencing can be used to identify the methylation / acetylation state of the DNA, which can then be converted into the transcriptional activity of the DNA. This has become possible with the advances from PacBio and Nanopore sequencing technologies. Second generation sequencing can also be used to identify methylation. By undergoing bisulfite conversion, this sequencing process can be used to determine the transcriptional activity of a DNA sequence. This is an indirect process, requiring library preparation prior to sequencing, and so it is therefore easier to use the more modern third generation technologies.