Certain epigenetic marks influence gene expression so strongly that they have acquired firm associations. Specifically, some histone modifications correlate with transcriptional activation, and some with transcriptional repression. Yet the absence of histone modifications isn’t entirely inconsistent with gene expression. Some exceptions have been observed. In fact, exceptions of this kind may be the rule in embryos, where chromatin marks appear to be irrelevant for regulating genes that are expressed in a punctual manner during development.
This finding is highlighted in this month’s issue of Nature Genetics. The cover feature—“Absence of canonical marks of active chromatin in developmentally regulated genes”—makes the case that unmarked chromatin permits rapid gene activation and deactivation during development, whereas chromatin marking helps maintain stable production of RNA. This view contrasts strongly with generally accepted ideas of how chromatin marks regulate gene expression.
“[We] show that the transcription of genes temporally regulated during fly and worm development occurs in the absence of canonically active histone modifications,” wrote the study’s authors. “Conversely, strong chromatin marking is related to transcriptional and post-transcriptional stability, an association that we also observe in mammals.”
The study was co-led by Roderic Guigó, a researcher affiliated with the Center for Genomic Regulation Pompeu Fabra University, and Montserrat Corominas, a researcher affiliated with the University of Barcelona.
“We didn't set out to study the relationship between the epigenetic chromatin marks and gene expression during development, but rather to analyze the function of these marks in DNA processing, said Corominas. “But we soon saw that there were some highly expressed genes that did not have the epigenetic marks on their chromatin—which are thought to be required to maintain such high levels of expression.
“We first considered that this could be an experimental artifact, since it is common for developmental genes to be expressed only in a few specific cells, which could lead to the signals from the marks being diluted out and not detected. However, when we analyzed the data from the modENCODE project, we realized that the genes that were regulated during development were indeed expressed even though they lacked the chromatin marks one would expect. A lot of our work has focused on experimentally confirming these results.”
Embryonic development is a well-studied process in which the precise regulation of gene expression is critical, since many genes are expressed simultaneously and in a punctual manner. The work from these two research groups in Barcelona now offers novel information for understanding this process, by focusing on a set of genes that act during development and are specific to certain tissues.
“At the present, we already have computer models that help us to predict the patterns of expression for genes based on their chromatin modifications. Our work now adds a new aspect that was previously not even contemplated, which will help us to make predictive models even more reliable,” explained Guigó. “Our results are based on the expression of genes in two model organisms. Now we have to see whether what we observed in these two organisms also holds true for humans. If so, the results from our study will be useful for improving approaches to manipulate or modulate the levels of gene expression—which would be extremely useful for studying and treating those diseases that we know are caused by the expression of specific genes.”