Synthetic and genomic regulatory elements reveal aspects of cis-regulatory grammar in mouse embryonic stem cells.

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 cis-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 cis-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 occ

SUBMITTER: King DM 

PROVIDER: S-EPMC7077988 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature