Transcriptional enhancers are critical for development, phenotype evolution and often mutated in disease contexts; however, even in well-studied cell types, the sequence code conferring enhancer activity remains unknown.
These findings reveal a TFBS diversity threshold overrides the need for optimized regulatory grammar and individual TFBS that bind specific master regulators.
Sequence variation in transcriptional enhancers modulates inter and intra-species phenotypic divergence due to changes in gene expression
It is known that transcription factor binding sites (TFBS) are required for enhancer function, and that transcription factors, modulate enhancer activity in a cell type specific manner; however, the precise sequence code conferring enhancer activity in each cell type remains unknown.
more than ten different TFBS are required for activity equivalent to a native enhancer, and […] these TFBS can be drawn randomly from a large repertoire.
Determining the repertoire of specific TFBS important for enhancer activity in different cell types will inform a more mechanistic understanding of how specific enhancer SNPs affect gene expression and are linked to disease.
Common Design 