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Images of species analysed in this study: European sea bass (Dicentrarchus labrax), puffer fish (Tetraodon nigroviridis), frog (Xenopus tropicalis) and Human (Homo sapiens). Conrad Waddington, considered the father of epigenetics, appears in the last photo (Source: ICM-CSIC).

New clues to analyse gene expression through epigenetics

Researchers from the Centro Nacional de Análisis Genómico (CNAG-CRG), based in the Barcelona Science Park, and the Institut de Ciències del Mar (ICM-CSIC) have shown that the DNA region known as the first intron, a region to which not much attention had been paid until now, is a key region for analysing gene expression by epigenetic modifications. Anna Esteve-Codina, data analyst of the Functional Genomics team at the CNAG-CRG, is co-author of the paper.


Epigenetics, the study of heritable changes in gene expression that don’t involve changes in the DNA sequence, is an extraordinarily active research field in biology nowadays. Epigenetic modifications integrate environmental and genetic information to give a certain phenotype (the set of characteristics showed by an individual) and can be transmitted from generation to generation, making it possible for characters acquired by environmental influence to be inherited and passed on to the descendants.

The most studied epigenetic modification is DNA methylation in promoter regions (those regulating gene expression), which is associated with gene silencing. However, this ‘more DNA methylation, more gene silencing’ rule is not always accurate, confusing researchers. The article counts on Dafni Anastasiadi as first author, researcher at ICM-CSIC, with the collaboration of Anna Esteve-Codina, data analyst of the Functional Genomics team at the CNAG-CRG and has been directed by Francesc Piferrer, research professor at ICM-CSIC.

“From the CNAG-CRG we have analyzed the RNA sequencing data and helped in the interpretation of the integration of the expression data with the epigenomic data. The fact that the methylation of the first intron is linked to the expression of the gene can be an indication that in this there are regulatory marks that modulate gene expression regardless of the promoter, which is the area that had been studied in gene expression until now”, says Ana Esteve-Codin, coauthor of the paper.

A universal mechanism in vertebrates

For this finding, researchers compared methylation and gene expression levels in European sea bass tissues of very different cellular and transcriptomic complexity. The study shows that this mechanism is universal, at least in vertebrates, since, in addition to sea bass tissues, tissues of other fish, amphibians and even human were analysed obtaining the same result: the first intron region is more informative and consistent than the promoter region to determine gene expression.

These results, due to their universality, have application in other fields of epigenetics research, such as the study of the response of organisms to environmental changes-marine environmental epigenomics is considered a promising research field-, developmental biology and the epigenetic changes associated with cancer-related processes. This study helps to focus the research efforts on the first intron as the most informative DNA region regarding the effects of methylation on gene expression.

Reference article: Anastasiadi, D.; Esteve-Codina, A.; Piferrer, F. (2018). “Consistent inverse correlation between DNA methylation of the first intron and gene expression across tissues and species“. Epigenetics & Chromatin 11: 37. DOI: 10.1186/s13072-018-0205-1