Functional Dissection of the Enhancer Repertoire in Human Embryonic Stem Cells

Abstract

Enhancers are genetic elements that regulate spatiotemporal gene expression. Enhancer function requires transcription factor (TF) binding and correlates with histone modifications. However, the extent to which TF binding and histone modifications functionally define active enhancers remains unclear. Here, we combine chromatin immunoprecipitation with a massively parallel reporter assay (ChIP-STARR-seq) to identify functional enhancers in human embryonic stem cells (ESCs) genome-wide in a quantitative unbiased manner. Although active enhancers associate with TFs, only a minority of regions marked by NANOG, OCT4, H3K27ac, and H3K4me1 function as enhancers, with activity markedly changing under naive versus primed culture conditions. We identify an enhancer set associated with functions extending to non-ESC-specific processes. Moreover, although transposable elements associate with putative enhancers, only some exhibit activity. Similarly, within super-enhancers, large tracts are non-functional, with activity restricted to small sub-domains. This catalog of validated enhancers provides a valuable resource for further functional dissection of the regulatory genome.

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Cited by papers we hold 3

• Deciphering regulatory DNA sequences and noncoding genetic variants using neural network models of massively parallel reporter assays. · 2019
  Not checked
• Functional evaluation of transposable elements as enhancers in mouse embryonic and trophoblast stem cells · 2019
  No notice
• High-resolution genome-wide functional dissection of transcriptional regulatory regions and nucleotides in human · 2018
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