Tahsin Stefan Barakat, Florian Halbritter, Man Zhang, André F. Rendeiro, Elena Perenthaler et al.
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.
Tahsin Stefan Barakat, Florian Halbritter, Man Zhang, André F. Rendeiro, Elena Perenthaler, Christoph Bock, Ian Chambers. Functional Dissection of the Enhancer Repertoire in Human Embryonic Stem Cells. 2018-07-19. https://doi.org/10.1016/j.stem.2018.06.014
This experiment summarizes ChIP-STARR-seq activity measured in naive H9 hESCs using STARR-seq plasmid libraries generated from naive H9 chromatin, including H3K27ac, H3K4me1, NANOG, OCT4, and input-enriched libraries. For each hg19 scaffold region, the processed RPP value is the region-level activity reported in Table S2, and the table retains both active and inactive regions for comparative enhancer analysis.
This experiment summarizes ChIP-STARR-seq activity measured in primed H9 hESCs using episomal STARR-seq plasmid libraries made from H3K27ac, H3K4me1, NANOG, OCT4, and input-enriched chromatin. For each hg19 scaffold region, the processed RPP value is the region-level activity reported in Table S2, and the table retains both active and inactive regions for comparative enhancer analysis.
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