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Nat Commun. 2018 Oct 26;9(1):4472. doi: 10.1038/s41467-018-06962-z.

Determinants of promoter and enhancer transcription directionality in metazoans.

Author information

1
Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, 13125, Berlin, Germany.
2
Department of Biology, Humboldt Universitaet zu Berlin, 10115, Berlin, Germany.
3
Department of Nephrology and Immunology, Faculty of Medicine, RWTH Aachen University, Pauwelstraat 30, 52074, Aachen, Germany.
4
Department of Biostatistics & Bioinformatics, Duke University Medical Center, Durham, 27710, NC, USA.
5
Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, 13125, Berlin, Germany. scott.lacadie@mdc-berlin.de.
6
Berlin Institute of Health (BIH), Berlin, 10178, Germany. scott.lacadie@mdc-berlin.de.
7
Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, 13125, Berlin, Germany. uwe.ohler@mdc-berlin.de.
8
Department of Biology, Humboldt Universitaet zu Berlin, 10115, Berlin, Germany. uwe.ohler@mdc-berlin.de.
9
Department of Biostatistics & Bioinformatics, Duke University Medical Center, Durham, 27710, NC, USA. uwe.ohler@mdc-berlin.de.
10
Berlin Institute of Health (BIH), Berlin, 10178, Germany. uwe.ohler@mdc-berlin.de.

Abstract

Divergent transcription from promoters and enhancers is pervasive in many species, but it remains unclear if it is a general feature of all eukaryotic cis regulatory elements. To address this, here we define cis regulatory elements in C. elegans, D. melanogaster and H. sapiens and investigate the determinants of their transcription directionality. In all three species, we find that divergent transcription is initiated from two separate core promoter sequences and promoter regions display competition between histone modifications on the + 1 and -1 nucleosomes. In contrast, promoter directionality, sequence composition surrounding promoters, and positional enrichment of chromatin states, are different across species. Integrative models of H3K4me3 levels and core promoter sequence are highly predictive of promoter and enhancer directionality and support two directional classes, skewed and balanced. The relative importance of features to these models are clearly distinct for promoters and enhancers. Differences in regulatory architecture within and between metazoans are therefore abundant, arguing against a unified eukaryotic model.

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