Determinants of promoter and enhancer transcription directionality in metazoans

Mahmoud M. Ibrahim, Aslihan Karabacak, Alexander Glahs, Ena Kolundzic, Antje Hirsekorn, Alexa Carda, Baris Tursun, Robert P. Zinzen, Scott A. Lacadie () and Uwe Ohler ()
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Mahmoud M. Ibrahim: Max Delbrück Center for Molecular Medicine
Aslihan Karabacak: Max Delbrück Center for Molecular Medicine
Alexander Glahs: Max Delbrück Center for Molecular Medicine
Ena Kolundzic: Max Delbrück Center for Molecular Medicine
Antje Hirsekorn: Max Delbrück Center for Molecular Medicine
Alexa Carda: Duke University Medical Center
Baris Tursun: Max Delbrück Center for Molecular Medicine
Robert P. Zinzen: Max Delbrück Center for Molecular Medicine
Scott A. Lacadie: Max Delbrück Center for Molecular Medicine
Uwe Ohler: Max Delbrück Center for Molecular Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06962-z

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