Cohen et al. found that of a pair of co-expressed genes only one promoter has an Upstream Activating Sequence (UAS) associated with that expression pattern. They suggested that UASs can activate genes that are not in immediate adjacency to them. This explanation could explain the co-expression of small clusters, but many clusters contain to many genes to be regulated by a single UAS.
Chromatin changes are a plausible explanation for the co-regulation seen in clusters. Chromatin consists of the DNA strand and histones that are attached to the DNA. Regions were chromatin is very tightly packed are called heterochromatin. Heterochromatin consists very often of remains of viral genomes, transposons and other junk DNA. Because of tight packing the DNA is almost unreachable for the transcript machinery, covering deleterious DNA with proteins is the way in which the cell can protect itself. Chromatin which consists of functional genes is often an open structure were the DNA is accessible. However, most of the genes are not needed to be expressed all the time.
DNA with genes that aren't needed can be covered with histones. When a gene must be expressed special proteins can alter the chemical that are attached to the histones (histone modifications) that cause the histones to open the structure. When the chromatin of one gene is opened, the chromatin of the adjacent genes is also until this modification meets a boundary element. In that way genes is close proximity are expressed on the same time. So, genes are clustered in “expression hubs”. In comparison with this model Gilbert et al. (2004) showed that RIDGEs are mostly present in open chromatin structures.
However Johnidis et al. (2005) have shown that genes in the same cluster can be very differently expressed. How eukaryotic gene regulation, and associated chromatin changes, precisely works is still very unclear and there is no consensus about it. In order to get a clear picture about the mechanism of gene clusters first the workings chromatin and gene regulation needs to be illuminated.
Furthermore, most papers that identified clusters of co-regulated genes focused on transcription levels whereas few focused on clusters regulated by the same transcription-factors. Johnides et al. discovered strange phenomena when they did.