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The grammar of transcriptional regulation

Abstract

Eukaryotes employ combinatorial strategies to generate a variety of expression patterns from a relatively small set of regulatory DNA elements. As in any other language, deciphering the mapping between DNA and expression requires an understanding of the set of rules that govern basic principles in transcriptional regulation, the functional elements involved, and the ways in which they combine to orchestrate a transcriptional output. Here, we review the current understanding of various grammatical rules, including the effect on expression of the number of transcription factor binding sites, their location, orientation, affinity and activity; co-association with different factors; and intrinsic nucleosome organization. We review different methods that are used to study the grammar of transcription regulation, highlight gaps in current understanding, and discuss how recent technological advances may be utilized to bridge them.

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Acknowledgments

This work was funded by grants to E.S. from the National Institute of Health (NIH) and the European Research Council (ERC). S.WG. is a Clore scholar.

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Correspondence to Eran Segal.

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Weingarten-Gabbay, S., Segal, E. The grammar of transcriptional regulation. Hum Genet 133, 701–711 (2014). https://doi.org/10.1007/s00439-013-1413-1

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Keywords

  • Regulatory Element
  • Nucleosome Position
  • Grammatical Rule
  • Nucleosome Formation
  • Predict Gene Expression