Journal
CELL SYSTEMS
Volume 11, Issue 1, Pages 75-+Publisher
CELL PRESS
DOI: 10.1016/j.cels.2020.05.011
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Funding
- National Institutes of Health [DP2GM114829]
- National Science Foundation Brain Initiative [1556207]
- Searle Scholars Program
- U.S. Department of Energy [DE-FC02-02ER63421]
- Ruth L. Kirschstein National Research Service Award [GM007185]
- USPHS National Research Service award [5T32GM008496]
- UCLA
- Direct For Biological Sciences
- Division Of Integrative Organismal Systems [1556207] Funding Source: National Science Foundation
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In eukaryotes, transcription factors (TFs) orchestrate gene expression by binding to TF-binding sites (TFBSs) and localizing transcriptional co-regulators and RNA polymerase II to cis-regulatory elements. However, we lack a basic understanding of the relationship between TFBS composition and their quantitative transcriptional responses. Here, we measured expression driven by 17,406 synthetic cis-regulatory elements with varied compositions of a model TFBS, the c-AMP response element (CRE) by using massively parallel reporter assays (MPRAs). We find CRE number, affinity, and promoter proximity largely determines expression. In addition, we observe expression modulation based on the spacing between CREs and CRE distance to the promoter, where expression follows a helical periodicity. Finally, we compare library expression between an episomal MPRA and a genomically integrated MPRA, where a single cis-regulatory element is assayed per cell at a defined locus. These assays largely recapitulate each other, although weaker, non-canonical CREs exhibit greater activity in a genomic context.
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