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bioRxiv · 10.1101/2021.10.21.465269

Systematic analysis of intrinsic enhancer-promoter compatibility in the mouse genome.

Martinez-Ara, M.·Comoglio, F.·van Arensbergen, J.·van Steensel, B.
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Abstract

Gene expression is in part controlled by cis-regulatory elements (CREs) such as enhancers and repressive elements. Anecdotal evidence has indicated that a CRE and a promoter need to be biochemically compatible for promoter regulation to occur, but this compatibility has remained poorly characterised in mammalian cells. We used high-throughput combinatorial reporter assays to test thousands of CRE - promoter pairs from three Mb-sized genomic regions in mouse cells. This revealed that CREs vary substantially in their promoter compatibility, ranging from striking specificity for a single promoter to quantitative differences in activation across a broad set of promoters. More than half of the tested CREs exhibit significant promoter selectivity. Housekeeping promoters tend to have similar CRE preferences, but other promoters exhibit a wide diversity of compatibilities. Higher-order TF motif combinations may account for compatibility. CRE-promoter selectivity does not correlate with looping interactions in the native genomic context, suggesting that chromatin folding and compatibility are two orthogonal mechanisms that confer specificity to gene regulation.

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Martinez-Ara, M., Comoglio, F., van Arensbergen, J., van Steensel, B.. 2021-10-22. Systematic analysis of intrinsic enhancer-promoter compatibility in the mouse genome.. https://doi.org/10.1101/2021.10.21.465269

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