The interplay of active and repressive histone modifications is assumed to have a key role in the regulation of gene expression. In contrast to this generally accepted view, we show that the transcription of genes temporally regulated during fly and worm development occurs in the absence of canonically active histone modifications. Conversely, strong chromatin marking is related to transcriptional and post-transcriptional stability, an association that we also observe in mammals. Our results support a model in which chromatin marking is associated with the stable production of RNA, whereas unmarked chromatin would permit rapid gene activation and deactivation during development. In the latter case, regulation by transcription factors would have a comparatively more important regulatory role than chromatin marks.

We thank the modENCODE project, the ENCODE Project (human and mouse data) and the Roadmap Epigenomics Mapping Consortium for granting open access of these resources to the scientific community. We also thank the Ultrasequencing Unit of the Centre for Genomic Regulation (CRG, Barcelona, Spain) for sample processing and the Confocal Unit of CCiTUB (Centres Científics i Tecnològics de la Universitat de Barcelona) (Universitat de Barcelona, Barcelona, Spain). This work was performed under the financial support of the Spanish Ministry of Economy and Competitiveness with grants BIO2011-26205 to R.G., CSD2007-00008 and BFU2012-36888 to M.C., and 'Centro de Excelencia Severo Ochoa 2013–2017', SEV-2012-0208 and the European Research Council/European Community's Seventh Framework Programme with grant 294653 RNA-MAPS to R.G. E.B. is supported by the European Commission's Seventh Framework Programme 4DCellFate grant 277899. J.C. is supported by grant SFRH/BD/33535/2008 from the Portuguese Foundation of Science and Technology