Non-canonical enhancers control gene expression and cell fate in human pluripotent stem cells

The preprint operates within the dominant paradigm of gene regulation, where enhancers play a crucial role in controlling gene expression. It specifically focuses on enhancers in human-induced pluripotent stem cells (hiPSCs).

This research refines the existing understanding of enhancers by identifying a class of “non-canonical enhancers” that lack typical characteristics like H3K27ac but still demonstrate enhancer activity. This challenges the current model of enhancer function, but it doesn’t represent a paradigm shift, rather a refinement within the normal science phase. The study uses established methods like STARR-seq, ATAC-seq, ChIP-seq, and CRISPR to investigate enhancer function and characterize these non-canonical enhancers. While the findings are significant and challenge some existing assumptions, they build upon the existing framework of gene regulation and enhancer function. The study expands the known repertoire of enhancers and suggests a more complex regulatory landscape than previously appreciated. This fits Kuhn’s description of normal science where research aims to puzzle-solve within the existing paradigm. Although the identification of non-canonical enhancers is novel, it does not fundamentally change the understanding of gene regulation or necessitate a complete rethinking of the field. It pushes the boundaries of the current paradigm but stays within its framework.