Synthetic and genomic regulatory elements reveal aspects of -regulatory grammar in Mouse Embryonic Stem Cells.

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ID: 94778
2020
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Abstract
In embryonic stem cells (ESCs), a core transcription factor (TF) network establishes the gene expression program necessary for pluripotency. To address how interactions between four key TFs contribute to regulation in mouse ESCs, we assayed two massively parallel reporter assay (MPRA) libraries composed of binding sites for SOX2, POU5F1 (OCT4), KLF4, and ESRRB. Comparisons between synthetic -regulatory elements and genomic sequences with comparable binding site configurations revealed some aspects of a regulatory grammar. The expression of synthetic elements is influenced by both the number and arrangement of binding sites. This grammar plays only a small role for genomic sequences, as the relative activities of genomic sequences are best explained by the predicted affinity of binding sites, regardless of binding site identity and positioning. Our results suggest that the effects of transcription factor binding sites (TFBS) are influenced by the order and orientation of sites, but that in the genome the overall occupancy of TFs is the primary determinant of activity.
Reference Key
king2020syntheticelife Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors King, Dana M;Hong, Clarice Kit Yee;Shepherdson, James L;Granas, David M;Maricque, Brett B;Cohen, Barak;
Journal eLife
Year 2020
DOI
10.7554/eLife.41279
URL
Keywords
systems biology mouse computational biology

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